Laboratory and clinical studies were performed on TA-058, a new semisynthetic penicillin antibiotic, and results were follows.
1) Antimicrobial activities
MICs of TA-058 against clinical isolates from our clinic were determined. With the inoculum size of 10⁶cells/ml, percentages of strains susceptible to 12.5μg/ml or less were S.aureus 89%, S.faecalis 86%, E.coli 37%, K.pneumoniae 0%, Enterobacter sp. 63%, S.marcescens 4%, Proteus sp. 79%, P.aeruginosa 8%. Antimicrobial activities agaist Gram-positive cocci were inferior to AMPC, but its activities againt Gram-negative bacilli were superior to AMPC.
2) Serum levels and urinary excretion rates
Three healthy adults were bolusly injected with 2g of TA-058, and mean serum levels of TA-058 were 283.3μg/ml at the end of the injection, 3.3μg/ml after 6 hours. Pharmacokinetic parameters calculated with these data were T1/2 (β) 1.3hr., AUC 202μg/ml·hr. Urinary excretion rates were 66 % during 6 hours. In a case of chronic renal failure, urinary excretion rate was very small and T1/2 (β) was lengthened.
3) Clinical efficacy
Nine patients with pneumonia, 3 with bronchitis, 1 with pulmonary tuberculosis, 7 with cystitis, 4 with pyelonephritis, 3 with bacteremia, 1 with meningitis, 1 with arthritis, and 1 with perianal abscess were treated with TA-058 daily at a dose of 1-8 g for 3-55 days. Clinical responses were excellent in 2 cases, good in 16, fair in 4, poor in 6, and unknown in 2 cases. Its efficacy rates were 54.5% in RTI, 72.7% in UTI, and 66.7% in other cases. One patient complained of vascular pain on the first trial of TA-058. GOT, GPT elevation was observed in 2 patients and ALP elevation in a case, who had previously liver damages.

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In vitro antimicrobial activity and clinical efficacy of TA-058, a newly developed parenteral penicillin, were evaluated.
The minimal inhibitory concentrations of TA-058 against clinical isolates, including S.aureus, S.faecalis, S.faecium, E.coli, K.pneumoniae, H.infiuenzae, P.mirabilis, S.marcescens and Enterobacter species, were compared with ampicillin (ABPC).
TA-058 was more sensitive than ABPC against P.mirabilis and H.infiuenzae, whereas less sensitive against S.aureus, S.faecalis and Enterobacter spp.
TA-058 was administered 2 patients with urinary tract infection and 6 with respiratory tract infection, including 4 with acute pneumonia, 1 with lung abscess and 1 with exacerbation of chronic bronchitis.
Total clinical efficacies were excellent in 1 case, good in 5 cases, fair in 1 case and poor in 1 case, respectively.
No side effect nor significant abnormality in laboratory data were observed.

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Serum concentrations of TA-058, a new parenteral penicillin, were measured after intravenous administration of 500mg dose to patients with stable end stage renal failure (on and off hemodialysis).
Mean serum concentrations of TA-058 between hemodialysis (n=2), 5, 30 minutes, 1, 6, 12, and 24 hours after i.v. injection were 50.0±12.6, 30.85±1.45, 26.0, 7.3±2.3, 2.0±0.8, and 0.35±0.05μg/ml, respectively, while those on dialysis (n=5), 5, 30 minutes, 1, 2, 4, and 6 hours after administration were 42.08±4.0, 23.88±2.41, 18.26±2.08, 12.26±1.43, 5.48±0.67, and 2.8±0.55μg/ml, respectively.
Pharmacokinetic parameters off and on hemodialysis, calculated by the mean serum concentrations were T 1/2 (β)=4.3, 1.9 hours, Kel=0.38, 0.68 hour^-1, Vd=19.21, 16.74 L, and AUC=132.3, 75.1μg/ml·hr, respectively.

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TA-058, a new semisynthetic penicillin, was studied clinically.
1) TA-058 was used in the treatment of 5 patients, consisting of 2 patients with bronchopneumonia, 1 with pyothorax, 1 with lung abscess and 1 with acute gingivitis. One strain of P.aeruginosa was cultured for potentially pathogenic organism. The clinical results were evaluated as good in 4 patients, fair in 1 patient.
2) As adverse effects which emerged during the course of TA-058 administration, elevation of GOT, GPT, LAP and γ-GTP was noticed in 1 patient and eosinophilia was noticed in 1 patient.

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Clinical efficacy of TA-058, a newly developed penicillin derivative, were evaluated in total 10 cases of patients, 4 cases with pneumonia, one with lung abscess, one with chronic bronchitis, one with cystitis, and 3 with secondary respiratory tract infection complicating lung cancer.
The clinical effects obtained were excellent in 3 patients, good in 2 patients, and fair in 2 patients. 3 patients could not be assessed clinically.
In bacteriological study, 2 strains of Haemophilus, 2 strains of P.aeruginosa were eradicated, 1 strain of K.oxytoca, 1 strain of E.cloacae were persisted.
Neither side effects nor adverse reactions on clinical laboratory findings attributable to the drug were observed.

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Laboratory and clinical studies on TA-058, a new penicillin, were carried out and resluts were as follows.
1) Antibacterial activity
Minimal inhibitory concentrations (MIC) of TA-058 for 272 strains isolated from various clinical materials (S. aureus 27, E. coli 27, K. aerogenes 27, E. cloacae 27, P. mirabilis 27, P. vulgaris 27, S. marcescens 27, P. aeruginosa 27, H. influenzae 56) were determined and compared with those of amoxicillin (AMPC). MIC of TA-058 against E. coli, E. cloacae, P. mirabilis and H. infiuenzae were 1-2 times higher than those of AMPC in general. On the other hand, MIC of TA-058 against S. aureus was 1-2 times lower than those of AMPC. Against the other organism, MICs of TA-058 were equal to those of AMPC.
2) Serum levels and sputum levels
In three patients with chronic respiratory infection, TA-058 was administrated by intravenous drip infusion. Peak serum levels were 44.5-67.5 pgiml at a dose of 1 g. The level ranged from 1.7-4.6μg/ml at five hours. Peak sputum levels of TA-058 were 4. 0-6.6μg/ml, but in one case peak sputum level was only 0.17μg/ml.
3) Clinical results and side effect Fourteen patients with respiratory tract infections (acute pneumonia 7, chronic bronchitis 4, lung abscess 2, bronchiectasis 1) were treated with TA-058 by intravenous drip infusion. Eight of the fourteen patients responded satisfactorily to the treament and the efficacy rate was 57.1%(8/14)(excellent 2, good 6, poor 3, not evaluable 3). No side effect and abnormality in laboratory findings were observed in any cases.

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TA-058 is a new semisynthetic penicillin which has a unique chemical structure containing an amino-acyl (N-methyl-asparaginyl) function in its side chain. Clinical and laboratory study has been performed on TA-058 in order to evaluate its usefulness mainly in respiratory tract infections.
Minimal inhibitory concentrations (MICs) of TA-058 against 27 strains of respiratory pathogenic H. influenzae sensitive to ampicillin were ≤0.013-0.1μg/ml. MICs of TA-058 against 22 strains of S. pneumoniae were 0.025-0.1μg/ml. MICs of TA-058 against respiratory pathogenic P. aeruginosa and K. pneumoniae were 0.39>100μg/ml and 0.78>100μg/ml, respectively. The synergistic effects were demonstrated between TA-058 and clavulanic acid or CP-45899 against respiratory pathogenic β-lactamase-producing ampicillin-resistant H. influenzae and B. catarrhalis.
Ratios of maximum sputum level to peak serum concentration ranged from 3.07% to 7.45% in 6 patients with chronic respiratory infections, while ratio of maximum intrabronchiolar level to peak serum concentration was as high as 20.1% in a patient with chronic bronchitis.
TA-058 was administered by the intavenous drip infusion of a dose of 1g twice a day. Eighteen respiratory tract infections and 10 urinary tract infections were subjected to clinical evaluation of TA-058, indicating favorable clinical response, i. e., the rates of clinical therapeutic efficacy were 94.4% and 80%, respectively. None of them showed adverse effects. The safety of this penicillin antibiotic was very good.
From the above results, it was concluded that TA-058 is one of the most effective and useful antibiotics for the treatment of the respiratory bacterial infections, particularly for those due to H. influenzae and S. pneumoniae.

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TA-058, a new semisynthetic penicillin derivative, was studied fundamentally and clinically, and the following results were obtained.
1) Antibacterial results
The antibacterial activity against S. aureus, E. coli, E. cloacae, K. pneumoniae and P. aeruginosa were examined, TA-058 was more active than that of CBPC but somewhat less active than that of PIPC.
2) Clinical results
TA-058 was used in the treatment of 6 cases with respiratory tract infections. The clinical results were evaluated as excellent in 3 cases, good in 2 cases and poor in one case.
3) Side effects
No side effects nor any abnormalities in laboratory findings were noticed. In conclusion, TA-058 seems to be a safe and useful drug in practice.

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A new semisynthesized penicillin TA-058 for parenteral use, with broad spectrum for gram positive and negative bacteria, was administered to 21 hospitalized patients with infection of abdominal organs: 12 with acute appendicitis, 5 with cholecystitis and cholangitis, 3 with acute panperitonitis and intestinal obstruction due to abdominal cancer and one with duodenal ulcer. TA-058 at a dose of 1 g was given by intravenous bolus injection before or during operation. Tissue specimens of different sites were taken from the surgically removed organs. Samples of purulent ascites and the biles were subsequently taken at intervals.
TA-058 concentration was determined according to a plate agar well bioassay method with M. luteus ATCC 9341 or E. coli ATCC 27166 as the test organisms.
The levels of TA-058 in the common duct bile increased quickly after injection and reached to the peak about at 1 hr. and then declined very slowly. That of the peak level was 520.0μg/ml and the mean level was 256.74±131.79μg/ml (5 cases, n=12) at 28 to 166 min. after the administration. In cases of obstructed cystic duct, TA-058 was observed in the gall bladder bile through the gall bladder wall, the peak level was 29.4μg/ml and the mean level was 11.67±17.29μg/ml (2 cases, n=4) at 13 to 197 min. after injection. In cases of opened cystic duct, which reached 285.0μg/ml, that was higher than in the common duct bile, and the mean was 172.0±80.19μg/ml (2 cases, n=4) at 125 to 178 min. after injection. TA-058 peak level in gall bladder wall was 32.7μg/g and the mean level was 16.3±9.44μg/g (5 cases, n=7) after i. v. TA-058 level in the infected appendix wall was directly proportional to degree of severity of inflammation, that the mean level was 9.22±14.61μg/g (12 cases) at 15 to 103 min. after i. v. TA-058 observed quickly in purulent ascites and stayed high levels for a long time. In purulent ascites of panperitonitis, TA-058 levels were trace, 0.83, 8.3, 48.0, 44.0 and 43.3μg/ml at 0, 1, 2, 53, 63, 70 min. after injection, respectively. The mean level of purulent ascites was 26.42±17.44μg/ml (4 cases, n=15) at 0 to 70 min. after i. v. In cases of empyemic appendicitis, TA-058 level in the pus in appendix wall was higher than which in appendix wall itself. The mean level was 11.23±7.79μg/ml (3 cases) after i. v.
These results were suggested, TA-058 gives prolonged high concentrations in the bile, purulent ascites and the infected tissues satisfactory for relatively long time, that were higher than the MICs against pathogenic bacteria, particularly E. coli and K. Pneumoniae.
For this reason, TA-058 is one of the preferred drugs for treatment of abdominal infections.

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A new semisynthesized penicillin, TA-058 for parenteral use, having broad spectrum for grampositive and gram negative bacteria and better responses has in vivo more than in vitro effect, was administered to a total of 30 patients. Those were 10 outpatient cases of acute infectious diseases of skin and soft tissues, 20 hospitalized cases of abdominal infectious diseases (15 with acute peritonitis and 5 with acute or subacute cholecystitis and cholangitis). TA-058 was given by intravenous bolus injection once a day for outpatients at a dose of 1 g and for hospitalized patients, it was given at a dose of 1 to 2 g by intravenous drip infusion twice or 3 times a day for 3 to 10 days. The clinical efficacy obtained was excellent 11 cases, good in 18 cases, fair in no case and poor in one case. Clinical adverse effect was not recognized.
Therefore, TA-058 appears to be a very useful drug that used for chemotherapy on acute peritonitis and biliary tract infection.

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The laboratory and clinical studies on TA-058 were carried out. TA-058 has antibacterial activity against Staphylococci, S. faecalis, E. coli, K. pneumoniae, E. cloacae, P. aeruginosa.
As for the results, TA-058 was equal to CBPC, SBPC, TIPC, PIPC against coagulase positive Staphylococci, inferior to PCG, ABPC. Antibacterial activity against coagulase negative Staphylococci was equal to CBPC, SBPC and it was superior by one grade to TIPC, inferior to another PCs.
The activity against S. faecalis was superior to CBPC, SBPC, TIPC by 2-3 grade, but inferior to ABPC, PCG, PIPC.
TA-058 was active as PIPC, ABPC against E. coli and was more active than CBPC and SBPC. Against K. pneumoniae it was equal to ABPC and against E. cloacae it was inferior by 3-4 grade to PIPC. TA-058 had same activity to CBPC against P. aeruginosa, but was inferior to SBPC, TIPC and PIPC.
Bile levels of TA-058, PIPC and CEZ in the rat were measured after intramuscular administration (20mg/kg).
Bile levels of TA-058 as follows were found: 15 min. 92, 30 min. 391, 1 hr. 340, 2 hr. 70μg/ml in average and bile levels of CEZ were as follows were found: 15 min. 93, 30min. 142, 1 hr. 90, 2 hr. 12μg/ml and concentration of PIPC were 2, 650, 3, 000, 1, 630, and 534μg/ml.
Bile levels of TA-058 after intraperitoneal administration were higher than those of intramuscular administration by double times.
TA-058 was administered to 14 cases of infections (respiratory tract infections 3, peritonitis 3, biliary tract infections 2, wound infection 1).
Results obtained were good in 11 cases, failure in 3 cases.
No marked side effects were observed throughout the clinical trials.

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Fundamental and clinical studies of TA-058 were carried out and the following results were obtained.
Antimicrobial spectra of TA-058 were similar to that of ABPC. Antimicrobial effect against clinical isolates were as follows: as effective as CBPC, SBPC and APPC against S. aureus, equal to CBPC and superior to SBPC against S. epidermidis, inferior to ABPC but superior to the other antibiotic injections against S. faecalis. Against E. coli, K. pneumoniae, E. cloacae, S. marcescens, P. mirabilis, and B. fragilis, TA-058 has similar antimicrobial effect to ABPC. No clinical application could be conceived against P. aeruginosa.
Serum and urinary concentrations were examined in three healthy male adults. Concentrations of TA-058 were assayed either by cup-or disc method with B. subtilis ATCC 6633 as test organism and by high pressure liquid chromatography (HPLC). Maximum serum concentration was 180μg/ml by means of bioassay or 166.7μg/ml by means of HPLC at five minutes after single injection of 2, 000mg. Urinary concentration reached its maximum a half an hour after injection and its mean value was 10, 450μg/ml by bioassay and 10, 707μg/ml by HPLC. Mean recovery rate in urine during eight hours was 69.3% by bioassay and 67.0% by HPLC. Pharmacokinetic parameters of the serum concentrations assayed by HPLC were: K12, 0.79 (hr.^-1); K₂₁, 1.53 (hr.^-1); Kel, 1.04 (hr.^-1); T1/2 (β), 1.22 (hr.); Vd, 16.07 (L); AUC, 181.6 (ug/ml·hr.). Metabolism of TA-058 was proved to be excreted as unchanged form in urine by bioautography with thin layer plates. Tissue concentrations were examined by intramuscular injection in SD rats. TA-058 was transferred maximally into kidney, followed by serum, liver, heart, spleen and lung.
Clinical efficacy were examined in ten cases of surgical infection. Six cases were effective and one case was fair, showed 60% of effective rate. In two of them elevation of GOT and GPT were observed.

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Fundamental and clinical studies on TA-058, a newly synthesized penicillin, in the surgical field and the following results were obtained.
1) Antibacterial activity
MIC value of TA-058 was superior to CBPC against E. coli isolated from surgical wound but slightly inferior to PIPC. Antibacterial activity against Klebsiella was apt to resistance.
2) Biliary excretion
Bile concentrations of TA-058 were measured in 2 patients. Those of peak level after intravenous administration of 1g were 81μg/nil and 23μg/ml, which showed low level becauce of severe patients.
Bile excretion of TA-058 was included in the moderate group.
3) Clinical results
TA-058 was used in 37 cases of suriicaf infections and in 2 cases of prophylactic use against postoperative infection due to acute appendicitis. The results were excellent in 7 cases, good in 22 cases, fair in 3 cases and unknown 5 cases. Rate of clinical effectiveness was 90.6%.
No side effects could be found in any of cases.

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Biliary excretion and clinical efficacy in biliary tract infections of TA-058, a new penicillin antibiotic was reported that the antibacterial activity in vivo was more effective than in vitro, were studied and the following results were obtained.
1) Biliary concentration of TA-058 was compared with TIPC by crossover method. 1 g of each antibiotic was given intravenously to 2 patients who, had indwelling T-tubes. Both TA-058 and TIPC reached the peak biliary concentrations at 2 hours after their administrations. The peak biliary concentration of TA-058 and that of TIPC was 246.5μg/ml, 66.6μg/ml, respectively.
2) After i. v. administration of 1 g of TA-058, the mean concentration in gallbladder bile of 5 cases was 218.9μg/ml, and the mean concentration in the gallbladder tissues of 9 cases was 18.1μg/g.
3) TA-058, penicilloic acid and 5-epi-penicilloic acid were isolated and identified with highperformance liquid chromatographic (HPLC) method. Penicilloic acid and 5-epi-penicilloic acid were the metabolites of TA-058. The correlationship between chemical assay and bioassay results of the concentration of TA-058 in each bile was r=0.998.
The rates of the metabolites after i. v. administration of 1 g of TA-058 were 12.9-31.4%(average 24.6%), but after 3 weeks at -20°C conditions it showed an increase of about 30%.
4) TA-058 was administered intravenously at a dose of 1 g 2 times a day over 5-9 days in total of 22 cases including 11 cases of cholacystitis, 11 cases of cholangitis. The clinical results showed excellent in 3, good in 15, fair in 2, poor in 1 and unknown in 1 and the efficacy rate was 85.7%.
5) TA-058 was given to 38 cases including prophylactic use for postoperative infection, no side effects were observed.

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Fundamental and clinical studies on TA-058, a new injectable penicillin compound which was derived N⁴-methvl-D-asparacrinyl residue on side chain of amoxicillin. performed to abdominal infections, especially on peritonitis, and following results were obtained.
1) The transfer into ascitic fluid and serum concentration were investigated against 2 patients with peritonitis. The peak concentration of ascitic fluid was observed in 1-2 hours after intravenous administration of 1.0 g of TA-058, 66.0μg/ml and 74.0μg/ml, respectively. High concentration (20.0μg/ml, 18.2μg/ml) of ascitic fluid was maintained even after 6 hours.
2) TA-058 was treated in total of 27 cases with intra-abdominal infection; 18 cases of peritonitis, 6 cases of abdominal abscess and 3 cases of postoperative wound infection of the abdominal wall. The clinical efficacy was excellent in 5 cases, good in 13, fair in 4 and poor in 3, with an effectiveness rate of 72.0%.
3) In bacteriological effects, the treatment provided eradication of E. coil, S. faecalis and Bacteroides sp., while P. aeruginosa partially persisted.
4) No serious side effects were observed.

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TA-058, a new semisynthetic penicillin, was tried in the field of surgery. Serum levels, bile concentration and urinary excretion were investigated on 5 patients with gallstone, and its clinical effectiveness including side effects was also investigated 15 patients. The results obtained were as follows:
1. Serum levels reach to their peak levels ranging from 80.5μg/ml to 42.7μg/ml, averaged 58.4μg/ml. in half an hour after single shot intravenous injections of 1 g of TA-058 in 20 ml of 20% glucose solution into 5 patients and lasted 6 hours, decreasing gradually to the average level of 5.5μg/ml.
Bile concentrations were assayed in 3 of 5 patients mentioned above. They varied with cases, showed their peaks one hour after injections in 2 cases, while in another case 3 hours after injection, showing the concentration of 14.0μg/ml, 34.3μg/ml and 130μg/ml respectively and lasted 5 to 7 hours.
Total urinary excretion of the drug was 889 mg (88.9%) on the average within 8 hours.
2. TA-058 was given to 15 patients with various surgical infections. The clinical results were excellent in 5 patients, good in 7, fair in one, poor in 2 and the efficacy rate was 80%.
3. No side effect was noticed except a slight elevation of GPT in one case of postoperative wound infection after the drug administrations.

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A new semisynthetic penicillin TA-058 has been studied. Basic and clinical efficacy in the surgical field were made on. The results were as follows:
1. TA-058 showed relatively excellent antibacterial activities against S. aureus, E. coli and Enterobacter isolated from the surgical lesions. Against P. aeruginosa, the MIC of TA-058 was a little bit higher, so that the administration dosage and method of TA-058 to the infections due to this organism were necessary to be scrutinized in the clinical field.
2. The biliary levels of TA-058 to the patients with drainage were examined. The concentration of TA-058 in bile showed a fluctuation according to the degree of blocked cystic ducts however TA-058 revealed the better transfer into bile.
Thus, a good therapeutic response can be expected against biliary tract infections.
3. The concentration of TA-058 in ascites just after operation of gastric tumor was also eninined.
The concentration reached to the maximum at 1 hour after intravenous administration of TA-058 2.0g and still, maintained fairly high levels for 4 hours.
The results revealed that TA-058 has the good transference into ascites.
4. TA-058 was administered to 8 cases with surgical infections, and the clinical response was excellent in 1 case, good in 5 cases, fair in 1 case and poor in 1 case.
No noteworthy side effect attributalble to the drug was observed.

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TA-058, a new semisynthetic penicillin derivative, has a broad antibacterial spectrum against gram-positive and gram-negative bacteria and also a potent bactericidal activity. Clinical evaluation of the drug in 9 cases of surgical infections was studied (3 with postoperative wound infection, one with intraabdominal abscess, one with intractable abdominal wall fistula, 3 with perineal infection after Miles' op. and one with pneumonia).
1.0 g of TA-058 was administered twice a day for 5-21 days by intravenous injection or intravenous drip infusion.
The results of clinical response were good in 6 cases, fair in one case and poor in 2 cases, Clinical efficacy rate was 66.7%.
In bacteriological response, 2 strains of Peptococcus, each one of α-Streptococcus, E. coli, E. cloacae, Neisseriaceae sp. and P.morganii were eradicated. 2 strains of S. aureus, one of E.coli and P. mirabilis were decreased. One strain of S. aureus, S. marcescens and B.fragilis remained unchanged. Eradication rate was 50.0 %.
No Side effects nor adverse reactions on clinical laboratory findings attributable to the drug were observed.

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The experimental and clinical studies on TA-058 were carried out. The results were as follows.
(1) Antibacterial activity
TA-058 has broad spectrum for GPC and GNR as well as other penicillins.
(2) Clinical effects
Two of three patients with acute simple pyelonephritis administered with daily doaes of 2 g of TA-058 for 5 days showed excellent efficacy. MIC of E. coli with one poor case was >100 μg/ml. This result has shown the high efficacy of TA-058 for acute simple pyelonephritis. Eighteen patients with chronic complicated urinary tract infections were intravenously administered with daily doses of 2 g or 4 g of TA-058 for 5 days. Clinical response was excellent in 6 cases, good in 4 cases and poor in 8 cases. The efficacy rate was 56%. According to classification by type of complicated U.T.I., TA-058 has good efficacy in 4 th group.
(3) Side effect
TA-058 has very low toxicity. In this study, no abnormal findings were observed in hemogram, liver and renal functions.

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Clinical effect of TA-058, a newly developed synthetic arnoxicillin derivative, was studied in six patients with complicated urinary tract infections. TA-058 was administered at a dose of 1.0g by I.V. drip infusion or one shot injection twice a day for five days.
Clinical effectiveness was found good in tour cases and poor in two cases with chronic complicated cystitis and pyelonephriiis. Thus, the overall efficacy rate in chronic complicated utiliary tract infections was 66.7%.
Bacteriological effects were as follows: Two strains of E.coli, one strain of Klebsiella and one strain of S.faecalis were eradicated. But one strain of Pseudomonas and one strain of Serratia were not eradicated. Bacteriological efficacy was evaluated to be 66.7%.
During the treatment with TA-058, S-GOT and S-GPT levels elevated in one case within normal range. No other side effect was observed subjectively nor objectively.

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TA-058, a new semisynthetic penicillin, was administered to 26 cases with urinary tract infections. All patients received TA-058 of 2-4 g for 5 days. One case of acute simple pyelonephritis showed excellent result. The results obtained in 22 cases with complicated urinary tract infections were excellent in 4, moderate in 6 and poor in 12 cases, with efficacy rate of 45.5%. There was no relationship between daily dose and the frequency of favorable responses. In bacteriological responses, eradication of strains resulted in 12 (46.2 %) out of 26 strains.
Neither subjective symptoms nor abnormal laboratory findings to the drug were observed.

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Human pharmacokinetic and clinical evaluation of TA-058, a new synthetic penicillin preparation, were made and the following conclusions were obtained:
(1) As to the pharmacokinetics, after one hour drip infusion administration of 4g of TA-058 and carbenicillin in 4 healthy male volunteers (crossover test), the peak serum levels were yielded 224.4 μg/ml and 242.6 μg/ml at the end of infusion, respectively.
The half-life in serum was estimated to be 84.0 min. and 60.0 mm. The mean urinary recovery rates in 8 hours were 59.0 and 81.8%.
(2) Concentrations of TA-058 were examined in genital organs such as testis, epididymis and prepuce of phimosis. After intravenous injection of 1 g of TA-058, the levels in those tissues, were highest in epididymis and followed by the testis and prepuce of phimosis, and those concentrations ranged from 1/5 to 1/2 of the serum levels.
(3) TA-058 was administesrd to chronic complicated cystitis in 5 cases and chronic complicated pyelonephritis in 5 cases. Eight cases satisfied the requirements of “Criteria for Evaluation of Drug Efficacy in U. T. I.”. The results were excellent in 1 case, moderate in 1 case, and the effective rate was found to be 25%. Bacteriological test demonstrated that 3 strains out of 11 (27.3%) were eradicated by TA-058.
As TA-058 is hydrolyzed by β-lactamase, we concluded that it is necessary to administer this drug with β-lactamase inhibitor in chronic urinary tract infections.

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In pharmacokinetic study, the absorption and excretion of TA-058 was studied in 4 healthy adult males by cross over method with CBPC as a control. Serum levels of the two drugs were similar except for their biological half lives. Namely, the half life (T½(β)) of TA-058 was 1.2 hr. and it was a little longer than that of CBPC, 0.8 hr. In the assessment on the penetration into human prostatic fluids, the mean level of TA-058 in prostatic fluids was 0.4 μg/ml (n=3) with the fluid/serum ratio of 0.009 at 1 hr. after single administration of 2 g.
Forty three patients (34 U.T.I. 7 gonococcal urethritis (GU) and 2 acute epididymitis) were treated with IA-058 at a dose of 1-4 g per day. Against 10 cases of simple U.T.I.(7 cystitis and 3 pyelonephritis), 100% cure rate was obtained. In complicated U.T.I., the efficacy rate was 54.2 % by the evaluation method of U.T.I. committee. In all of 7 GU, excellent results were gained. Satisfactory response was noticed in 2 acute epididymitis cases.
Concerning the in vitro activity on the clinical strains isolated from the treated cases, TA-058 had greater activity on the strains of E. coil, and gram positive cocci, such as S. faecalis and S.epidermidis, but less activity on P. aeruginosa.
There was no apparent untoward reaction except for one case of transient nausea. In the results of clinical laboratory values, slight elevation of s-GOT and s-GPT was observed in 4 cases and slight elevation of BUN in one case. No abnormal value was found in hematological studies.
It is concluded that TA-058, a new member of parenteral penicillins, is a safe, well tolerable antibiotic drug and clinically useful on the infections caused by E. coli, and other enteric rod bacteria, in addition to gram positive cocci.

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Laboratory and clinical traials of TA-058, a new semi-synthetic penicillin, were performed and following results were obtaind.
1) A peak prostatic tissue level of 43.5 μg/g was achieved in prostatauxe after administration of 1 g.of, TA-058 intravenously and its ratio to the mean serum level was 27.0%.
2) The morphological alteration of S.warneri in urine exposed to TA-058 showed various situation with swelling, aggregation and normality.
In that of E. coli, TA-058 induced filamentation of the cells at low concentrations. Spheroplasts were formed with elevation of the concentration, and the filamentous cells were lysed.
3) The clinical rate of effectivness for 23 cases of acute simple cystitis was 91.3%, and that of 13 cases of complicated urinary tract infections was 38.5%.
4) Any serious side effects and abnormal laboratory findings were not observed.

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TA-058, a new semisynthetic penicillin antibiotic agent, was studied both fundamentally and clinically. Results obtained were as follows;
1) TA-058 was highly active against gram-positive bacteria and P. mirabilis.
2) Urinary recovery rate within 2 hours after intravenous bolus injection of, 1g of TA-058 in healthy volunteers was over 50 %. About 80 % of the dose was excreted in the urine within 12 hours. A peak urinary concentration of over 5, 000μg/ml was achieved after 2 hours.
3) Amoxicillin, a metabolite of TA-058 was detected in the urine of healthy volunteers by bioautogram and high performance liquid chromatography. Amount of, amoxicillin in the urine was 2 to 4 % of TA-058.
4) Eight patients with chronic complicated urinary tract infections were treated with 1g of TA-058 twice a day for 5 days by intravenous bolus injection. The overall clinical efficacy of the treatment was moderate in 2 and poor in 6 patients.
5) Neither subjective side effects nor aggravations in laboratory test results related to the TA-058 treatment were observed.

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1), Clinical effect of TA-058 was studied in 16 patients with complicated urinary tract infections.
2) The clinical results were excellent in 3 cases, moderate in 7 cases and poor in 6 cases. The effective rate was 63%.
3) On bacteriological evaluation TA-058 was the relatively good activity against Pseudomonas genus.
4) Serum levels and urinary excretion of TA-058 were measured in 4 patents. The serum level attached to the peak at 30 minutes and the urinary recovery rate up to 4 hours reached 50%.
5) Tissue concentrations of TA-058 to kidney (one case), bladder (2 cases) and ureter (one case) were investigated. After the intravenous bolus injection of 1 g, the concentrations achievedin kidney 67.5μg/g at 30 minutes, 122.5 μg/g at 60 minutes, in bladder 72.5μg/g and 69.0μg/g at 30 minutes and 135.0 μg/g and 41.5 μg/g at 60 minutes, in ureter 24.5 μg/g at 60 minutes.
6) No side effects were observed in all cases.

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TA-058 is a new semisynthetic derivative of amoxicillin. Twenty-seven patients suffering from genitourinary tract infections were treated with 1 or 2 g of TA-058, intravenously twice daily for days, and the clinical efficacy and safety were evaluated. Of these 27 patients, 3 had uncomplicated urinary tract infections (all with acute pyelonephritis), 13 complicated urinary tract infections (2 with chronic pyelonephritis and 11 with chronic cystitis) and 11 infections of the male genital organ (4 with acute epididymitis and 7 with acute prostatitis). An excellent response was obtained in 100 % of the patients with acute pyelonephritis, and excellent plus moderate response in 54% of the patients with complicated urinary tract infections and in 100 % of the patients with infections of the male genital organ. Two patients of diarrhea were noted as an adverse reaction. No additional laboratory abnormalities were found except a transient elevation of alkaline phosphatase in one patient. The administration of this drug was shown to be useful in managing genitourinary tract infections.

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Fundamental and clinical studies on TA-058, a new injectable penicillin derivative, were performed, and following results were obtained.
1) Antibacterial activities
Antibacterial activities against clinically isolated 8 spieces were investigated, and approximately TA-058 displayed near equal activity in MICs comparison with CBPC, but slightly less activity than PIPC.
2) Serum levels and urinary excretions
Serum levels and urinary excretions of TA-058 after i. v. drip infusion of 1, 000 mg were determined in 3 male healthy adult volunteers.
When comparison of infusion time for 1 hr. and for 2 hr. was examined in this trial, in the former case the peak serum concentration was 60.7μg/ml, while in the latter case 31.5μg/ml. Similarly the peak urinary concentration showed value of 2, 809.6 μg/ml and 3, 709.1 μg/ml. respectively.
Urinary recovery rate was 76.1% and 77.0% within 24 hr. after administration.
3) Clinical evaluations TA-058 was treated in 10 cases of acute simple cystitis and 45 cases of complicated urinary tract infections (UTI). The cure rate for acute simple cystitis was 100% and for complicated UTI was 38%.
The rate of bacteria eradication in acute simple cystitis was 100%, and that of in complicated UTI was 63%.
As for side effects (total subjects: 65 cases), a slight anaphylactoid shock was observed in one case, however the symptom was immediately recovered by fluid therapy. Laboratory findings showed elevation of transaminases in two cases.

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Six-teen patients with complicated urinary tract infection (12 patients) and acute epididymitis (4 patients) were treated with TA-058 intravenously (one-shot injection) at daily dose of 2-4g (twice a day) 5-10 days.
In 12 cases With chronic, complicated urinary tract infection, the results were excellent in one case, moderate in 7 cases, poor in 4 cases and the effectiveness rate was 66.7%. In 4 cases with acute epididymitis, all wet evaluated moderately.
Bacteriologloally, 17 strains (80. 9 %) were eradicated out of 21.
No subjective or objective side-effects were observed in any cases.

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Fundamental and clinical studies of TA-058 were performed and transfer of TA-058 into prostatic tissue was also scrutinized.
The following results were obtained;
1) Minimum inhibitory concentration of TA-058 was determined by plate dilution method on strains isolated from urinary tract infections. Antibacterial activities of TA-058 were markedly strong against P. mirabilis, moderately strong against E. coli and slightly weak K pneurnoniae, P. gulgaris and P.aeruginosa. However, S.marcescens was resistanoe to TA-058. As compaired with other penicillin derivatives, TA-058 was weaker than PIPC but equal or slightly strong than ABPC or CBPC in antibacterial activities.
2) Transfer of TA-058 into prostatic tissue to 13 patients with prostatectomy examined. Maximum concentration of TA-058 was observed 61. 5±28.5μg/g at 30 minutes after one shot intravenous administration of 2 g and still maintained 19.0±7.1μg/g at two hours after administration. Judging from its favorable tranfer into the prostatic tissue and MICs against clinically isolated S. aureus, S. faecalis, S epidermidis and P. mirabilis, TA-058 seemed to be clinically useful in the treatment of prostatic infections.
3) Twenty three cases with complicated urinary tract infections were treated with TA-058 and evaluated clinically by the criteria of U. T. I. committee. The group of 2 g daily (21 cases) resulted 28.5% of effective rate, whereas the group_of 4 g daily (2 cases) resulted 100% of effective rate. Bacteriologically, TA-058 showed superior antibacterial activities against gram-positive bacteria, Enterobacter, E. coli and P. mirabilis. 22 out of 34 strains were eradicated (eradicated rate: 64.7%). No noteworthy side effects attributable to TA-058 were observed.

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TA-058, a new semisynthetic penicillin, was investigated clinically in the urological field. Sixteen patients with complicated urinary tract infections were treated with 1-2 g i. v. of TA-058. Clinical efficacy was assessed according to the “Criteria for Clinical Evaluation in Complicated U. T. I.”.
The following results were obtained.
1) The clinical results were excellent in 3 cases, moderate in 4 cases, and poor in 9 cases. The overall clinical effectiveness rate was 43.8 %.
2) On bacteriological evaluation, of 22 isolates before treatment 14 were eradicated and eradication rated was 63.6 %. Relationship between MICs and eradication rated was not clarified in our study.
3) No side effects were observed in any cases.

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TA-058 was administered to 84 cases diagnosed as urinary tract infection among out-patients and in-patients of departments of urology of 15 institutes (i. e. Kyushu University and its related university and other hospitals) from July 1981 to January 1982. The patients were treated with 1-2 g of this drug per day in simple urinary infection, 2 g or 4 g per day in complicated urinary tract infection.
In case of simple urinary tract infection, the clinical effects of TA-058 were excellent in 8 cases and good in 2 cases out of 10 cases except for 2 drop out cases (effective rate 100 %). In case of Complicated urinary tract infection, its effects were excellent in 8 cases, good in 21 cases and poor in 38 cases out of 67 cases except for 5 drop out cases (effective rate 43.3 %).
Bacteriologically, 43 strains out of 85 strains isolated from all cases of complicated urinary tract infection were disappeared after treatment with TA-058. This drug was effective for gram positive bacilli, E. coli and P. mirabilis but not for Serratia and Klebsiella.
No side effects were noticed during the treatment with this drug but GOT and GPT elevation col laboratory findings was observed in only one case.

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1) TA-058 was administrated to 20 cases with complicated urinary tract infection.
2) The efficacy of the group given 2 g was assessed to be poor in all cases and the efficacy of the group given 4g was assessed to be excellent 1 case (10.0 %), moderate 3 cases (30.0 %) and poor in 6 cases (60.0 96), for an effectiveness rate of 40.0%.
3) In bacteriological results, out of 20 strains in the group given 2g 6 strains were eradicated (30.0%), : out of 16 strains in the group given 4g 8 strains were eradicated (50.0%).
4) No side effects were observed in all cases.

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TA-058 was intravenously administered to 9 patients with acute pyelonephritis at a daily dose of 2-4g for 5 days.
The results were summarized as follows;
1) As to, the overall, clinical efficacy, excellent response was seen in 33.3%, moderate in 44.4% and poor in 22.2%.
2) Pygria was cleared in 5, decreased in 2 and unchanged, in 2 cases.
3) Bacteriuria was eliminated in 3, decreased in 1, replaced in 1 and unchanged in 4 cases.
4) As to the bacteriological response to TA-058, 4 (36.4%) were eradicated and 7, (63: 6%) persisted out of, 11 strains isolated.
5) Side effects were in 1 of 9 cases. Subjective side effects were not observed, but one case of mild nausea.
From the above results, TA-058 was suggested to be a useful, drug in the treatment of acute pyelonephritis.

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MIC of TA-058 and AMPC against 210 strains of GNR including each 30 strains of E. coli, K pneumoniae, P. mirabilis, P. vulgaris, Enterobacter, S. marcescens and P. aeruginosa isolated from U. T. I. were measured by agar dilution method with inocutum size of 108/ml and 106/ml. Antibicterial, activity of TA-058 against E. coli showed two peaks of MIC distribution at 3.13μg/ml and higher than 100μg/ml. Antibacterial activities of TA-058 seemed to be one fold stronger than AMPC. Both drugs did not demonstrate strong activity against K pneurnoniae and P. mirabilis. Nevertheless, TA-058 was, a little superior than AMPC. P. vulgaris, Enterobacter and S. marcescens seemed to be resistant to both drugs. P. aeruginosa was not sensitive to this drug with 108/ml inoculum size but 19 out of 28 strains (67.896) distributed from 3.13μg/ml to 50 with 106 /ml inoculation.
Bolus injection of 2 g of TA-058 and SBPC was administered to 4 male healthy volunteers by cross-over method. Serum peak level was obtained 5 minutes after the injection, 148.3μg/ml for TA-058 and 202.5μg/ml for SBPC. Serum half-life of fl-phase of the drug was 1.5 hours, which was a little longer than that of SBPC. AUC of the two drugs ranged 191.2μg/ml·hr. and 219.1μg/ml·hr., respectively. trinary excretion rate of TA-058 and SBPC until 6 hours was measured as much as 81. 1% and 82.6%, respectively. Maximum urinary concentration was recorded at the first 1 hour urine, 16, 675μg/ml for TA-058 and 9, 875μg/ml for SBPC. TA-058 was administered to 22 patients with chronic U. T. I. I to 4g daily for 5 days. Overall clinical efficacy according to the 2 nd criterion recommended by Japanese U. T. I. committee was evaluated excellent in 6, moderate in 7 and poor in 9 cases, counting 59.1% of effectiveness rate.
Five strains of S.faicalis and a few of K. pneurnoniae, P. aeruginosa, E. coli, S. marcescens and other bacteria were cleared from the urine after the treatment.
No adverse subjective effect and abnormal clinical laboratory test were observed with this regimen.

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Fundamental and clinical evaluations of TA-058, a new semi-synthetic penicillin for injection, was carried out in the field of obstetrics and gynecology. In vitro antibacterial activities of TA-058 was not so characteristic compared with similar penicillins as far as from our results tested with clinical isolates such as E. coli, K. pneutnoniae, P. mirabilis, P. aeruginosa, S. aureus and S faecalis.
Placental transfer of TA-058 was favorable to some extent and umbilical cord serum concentration reached about a half of maternal serum concentration two hours after intravenous injection of 1.0 gram and also was observed transfer to amniotic fluid, whereas transfer to mother's milk was scarce.
In the clinical trial TA-058 was effective in 81.5 % of the patients tested which were Composedof 13 cases of female genital infections and 14 cases of urinary tract infections by 71.4 %. This might be reflected by relatively higher inclusion rate of complicated urinary tract infections compared with female genital infections which was mainly of moderate or mild cases. Furthermore these clinical results were viewed from the species of causative organisms and the type of infections either of single bacterial-or multiple bacterial infections.
No appreciable side effects were observed.

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TA-058, a newly developed penicillin, was evaluated id the field of obstetrics and gynecology, and the following results were obtained.
1) The antibacterial activity was determined in 15 species (70 strains) of clinical isolates. The sensitivity destribution ranged from 1.56 to 3.13 μg/ml in 27.2 % and 30 % with over 100 μg/ml.
2) As to the pharmacokinetics, concentration in serum was 34.7 μg/ml at 30 minutes after intravenous injection of 1 g. The half-life in serum estimated to be 78 minutes, and AUC was 64.6 μg/ml·hr. The urinary recovery rate was 58.1 % in 6 hours.
3) The tissue penetration of TA-058 in uterine artery serum, uterine and adnexal tissues after intravenous injection of 1 g were determined and pharmacokinetic analysis was performed. The peak serum concentration (C_max) in uterine artery serum was 24.4 μg/ml and the half-life (T1/2 (β)) was 56.8 min. C_max in each tissues were 10. 6-16.5 μg/g, Tmax were 42.9-52.6 min. and half-life (T1/2 (β)) were 45.2-55.3 min. The area under the curve (AUC) was 74.5 μg/mlμhr. in serum and were 25.8-41.4 μg/mlμhr. in each tissues. Penetration of TA-058 into intrapelvic genital organs was found to be good.
4) Rapid transference of TA-058 into the umbilical cord serum and amniotic fluid was observed after an intravenous injection of 1 g, and those levels were about 25-30 % of the mother's serum level.
5) Distribution of TA-058 into mother's milk after an intravenous injection of 1 g in puerperants was low.
6) TA-058 was administered intravenously to 10 cases of gynecoobstetrical infections with daily dose of 2-3 g. The good clinical responses were assessed in 9 cases and few side effects were observed. As for the laboratory findings, a little elevation of transaminase was observed in one case. These results indicates that TA-058 is a useful drug in the field of obstetrics and gynecology.

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One gram of TA-058, a parenteral penicillin, was given by intravenous single shot to each of 18 patients who underwent total hysterectomy suffered from myoma of the uterus, and the levels of TA-058 in sera of cubital vena and uterine artery, and cervix, myometrium, endometrium, ovarium and Fallopian tube were determined by bioassay method with E. coil ATCC 27166 and M. luteus ATCC 9341 as the test organisms.
Mean venous serum level after injection of one gram of TA-058 was, 39, 4 μg/ml at 30 min., 25.8μg/ml at 60 min., 23.0 μg/ml at 90 min., 11.3 μg/ml at 120 min., 9.5 μg/ml at 150 mm. and 3.7 μg/ml at 240 min., respectively. Mean serum level of the uterine artery wes nearly equal to mean level of venous serum at the same time.
The rates of tissue levels to serum levels at 30 min. after injection were 56.3 % in cervix, 50.5 % in myornetrium, 45.7 % in endometrium. 51.5% in fallopian tube and 42.0 % in ovarium, respedively.
Clinical effect, was estimated in nine cases, two cases of vaginal cuff abscess, one case of surgical wound infection, three cases of adnexitis and three cases of pelvic peritonitis. TA-058 was given by intravenous injection in five cases and dripping in four cases. Total doses ranged from ten to forty two grams. Clinical effect was obtained good in eight cases and poor in one case of adnexitis. The bacteriological effect was investigated in vivo, and found to be effective, in 57.1 % of all cases.
No adverse reaction was observed in any of the cases treated with TA-058, nor was there any marked changes in the laboratory findings including peripheral blood examinations, hepatic and renal function.

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Fundamental and clinical studies on obstetrical and gynecological use of TA-058 were performed with following results.
1. Following a single intravenots injection of 1.0 g, the transfer of TA-058 to the internal genital organs was found to be clinically sufficient. The transfer of TA-058 to exudateof the dead space of pelvis was also sufficient.
2. In clinical trial, TA-058 was administered to 15 patients, and it showed good efficacy in all patienta except two cases. No side effect was noted except eosinophilia in one case.

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Concentration of TA-058 was examined in peripheral vein, uterine artery and genital organs including ovary, oviduct, endorrietrium, myometrium, cervix uteri and portio vaginalis of 45 cases received simple hysterectomy or other gynecological operations. Data were analized by the simulation curves prepared from pharmacokinetic parameters using the two-compartment model.
No marked difference in concentration between peripheral vein and uterine artery was observed after administration of 2g dose intravenously. The half life of the former was 1.4 hours and that of the latter was 2 hours.
The peak level of TA-058 in Those genital organs was attained 34.1 to 58.4 μg/g during 0.21 to 0.52 hours. Some differences in half life among various tissues were observed. They were varied from 0.53 to 1 hours. Area under curves (AUG) of various tissues were achieved about 30 to 50% of that of uterine artery level.
From the above results, it is concluded that the transfer of TA-058 to genital organs was sufficient.

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TA-058, a new injectable penicillin, was evaluated pharmacologically and clinically in the field of obstetrics and gynecology.
In pharmacological studies, 1 g of TA-058 was intravenously administered to 7 cases prior to simple abdominal hysterectomy, and the concentrations of TA-058 after injection were determined in venous blood, arterial blood of uterus, uterine cervix, portio vaginalis, myometrium, endometrium, oviduct and ovary. The samples were collected during 37 min. to 187 min. after intravenous administration. The venous blood concentration of 4 cases ranged from 2.7μg/ml to 15.9μg/ml and die arterial blood concentration of 6 cases showed from 2.7μg/ml to 28.5 μg/ml.
TA-058 was administered to 10 cases of various types of bacterial infections and clinical efficacy was excellent in 5 cases, good in 4 cases and failure in one cases. Overall cure rate was 90.0 %. No side effects nor adverse reactions on clinical laboratory findings in blood and hepatic and renal function were observed.

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TA-058, a new semisynthetic penicillin derivative, was evaluated to obtaip the following results.
1) The in vitro activities of TA-058 against various strains of clinical isolates were compared with those of piperacillin, sulbenicillin and ampicillin. TA-058 showed relatively same activities as sulbenicillin against S. aureus, K. pneumqniae and S. marcescens. Against E. coli, TA-058 was stronger than sulbenicillin. It was the most active, against P. mirabilis, whereap less active against P.vulgaris.
2) TA-058 was administered to 4 cases of various types of infections, and clinical response was good 2. cases.and poor 2 cases. No serious side effect of adverse reaction was observed.

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Fundamental and clinical studies were performed on TA-058, newly developed Penicillin, and following results were obtained:
1) Maximum concentrations of TA-058 were observed immediately after intravenous drip infusion of 1 g TA-058 of 30 minutes' duration in both uterine arterial blood serum and female genital organic tissues; the concentrations were 98.0μ/ml in uterine arteries, 30.0μg/g in ovaries 41.6 μg/g in oviducts, 62.7 μg/g in endometriums, 48.5 μg/g in myometriums, 47.1μ/g in cervical supravaginal portions and 58.6 μg/g in cervical vagipal portions, respectively., The half lives of TA-058 were 1.8 hours in uterine arteries and within 0, 8 and 2. hours in female genital organic tissues.
2) Total, amounts of 10 to 30 g of TA-058 of 5 to days' duration were administered for 10 obstetrical and gynecological complicated infections, such as postoperative abdominal abscess, pyometra, vaginal stump abscess, retroperitoneal abscess, intrauterine infeciion, adnexitis and puerperal infections. Clinically, TA-058 were evident to be effective in 80 % of cases. Leukocytesis and increased blood sedimentation rates were significantly improved. No side effects were obserypd Bacteriologically, pathogens were eliminated in 50 % of cases and replaced in 30% f cases. In 20 % of cases, the pathogens were not determined following TA-058 administrations.
It was concluded that TA-058 was safe and effective antibiotics.

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Fundamental and clinical studies on TA-058 were carried out.
1) The MI ICs of TA-058 against bacteria clinically isolated from ORL infections were determined by usipg inoculum size of 10⁶ cells/ml. The peak MIC against 20 strains of S. aureus was 3.13 μg/ml. TA-058 also exhibited superior antibacterial activity against P. mirabilis, P. put refaciens and E. cloacaeof the MIC range of 0.24-0. 78 μg/ml.
2) The peak serum levels at one hour after intravenous injections of 0.5 g or 1. 0g were 12, 0 μg/ml and 37. 5 μg/ml, respectively. The high levels were maintained even after 6-8 hours.
3) At 60 minutes after intravenous njection of 0.5 g, the concentrations in the tonsil, adenoid, mucous membrane of maxillary sinus, nasal polyp and tissue from nasal cavity were about 3.5 μg/ml, respectively. In the case of g intravnous administration, the tissue concentrations were almost twice of the) levels in 0.5 g admiptist, ratione,
4) Thirty four cases with ORL infections were treated with TA-058. The therapeutic responses were excellent in 20 cases and good in 8 cases to calculate an efficacy rate of 82.3 %.
5) Neither appreciable side effects except for skin rash observed in one case, nor abnormal laboratory findings were noted.

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From the laboratory and clinical studies on TA-058, the following results were obstained.
1) Antibacterial activity of TA-058 was inferior to that of ABPC and equal to that of PIPC against S. aureus. On the other hand, against P. mirabilis; it was superior to that of all. But it was inferior to that of PIPC against K. Pneumoniae, indole positive Proteus sp. and P. aeruginosa.
2) Tissue concentation of TA-058 was determined 1 hour after intravenous injection in human. In case of 1, 000 mg dosing, the mean concentration was 2.57μg/g in tonsil.
3) TA-058 was used clinically in 24 cases of various infections in otorhinolaryngological field, and its efficacy rate was 83.3 %.
4) No side effects were observed in all cases.

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To 10 cases of otorhinolaryngological infectious diseases (tonsillitis acuta, peritonsillar abscess, auricular phlegmon acuta, purulent fistula auris congenita, otitis media chronica and its exacerbativa and purulent thyroiditis etc.) the drug was administered intravenously at 2 g per day for 5 days and the result shows that the remarkably effective cases were 20 %, effective cases 60%, slightly effective cases 10 % and ineffective cases 10 %.
Any side effect was not observed 404 it was demonstrated that it was effective against gram positive and negative microorganismus, having excellent effectiveness.

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Fundamental and clinical studies of TA-058, a new penicillin antibiotic, were performed in the fieradf ophthalmology, and the results obtained were as follows.
1) The bacteriological activities of TA-058 was similar to that of ABPC, CBPC and PIPC.
The distribution of the sensitivity for 20 clinical isolates of S. aureus was in the range of 0.78-12.5μg/ml and the peak were at 0.78 μg/ml and 3.13 μg/ml, and each number of strains were 5 (25 %) respectively. Ten strains of P. aeruginose were sensitive at 25->100 μg/ml and of these five were distributed under 50μg/ml.
2) Ocular penetrations were examined in the rabbit eye. After intravenous injection of 50 mg/kg the aqueous level reached the peak of 6.0 μg/ml after 1/2 hours. Aqueous serum ratio at 30 minutes was 5.28%. The ocular tissue concentrations at 30 minutes after intravenous injection showed high levels in outer parts of the eye and relatively high levels in inner parts.
3) In the clinical study, the intravenous injection or drip infusion of 1.0 g-2.0 g once or twice a day was performed in 14 cases, such as external hordeolum, meibomianitis, acute dacryocystitis, corneal ulcer, corneal abscess, iridocyclitis purulenta, orbital infection. The result obtained was excellent in 5 cases, good in 8 cases and poor in 1 case.
4) No abnormal findings were recognized and no severe side effects were observed.

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Experimental and clinical studies for ophthalmic use of TA-058, a new penicillin, were performed.
1) Rabbits were used for the experimental studies. After subconjunctival injection of TA-058 (300 mg/eye), the peak levels were 109.6 μg/ml at 30 minutes in serum level and 76.3 μg/ml at 15 minutes in aqueous humor. After intramuscular injection (100 mg/kg), the peak levels were 5.6 μg/ml at 1 hour in aqueous humor and 107.5 μg/ml at 30 minutes in serum. The peak level in aqueous humor after intravenous injection (100 mg/kg) was 8.4 μg/ml at 1 hour. When this drug was given by subconjunctival injection, relatively high level was observed in aqueous humor, and the aqueous humor/serum ratio at 15 minutes was 86.7 %.
The concentration of TA-058 in ocular tissues reached to the relatively high level by any route of the administration.
2) 4 patients with corneal abscess were treated with TA-058 to evaluate its clinical efficacy. In 3 cases, TA-058 was effective, while no improvement was found in 1 case with α-hemolytic streptococcus infection.
No side effect was observed with administration of TA-058.

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From clinical study of TA-058, the following results were obtained.
1) Total of 5 cases including cases of lid abscess, a case of panophthalmitis and 2 cases of hordeolum were treated with TA-058 and results were good in 3 cases and fair in 2 cases.
2) No side reactions were observed.

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In order to study the ophthalmological application of TA-058, fundamental and clinical investigations were carried out and the following results were obtained.
1) In rabbits, TA-058 was injected intravenously at the dosis of 50 mg/kg. The concentration of TA-058 in aqueous humor at 15 minutes after administration was 3.15 μg/ml and the ratio of concentration (aqueous humor/plasma) was 1.1 percent.
TA-058 showed very good penetration into ocular tissues, especially lid, bulbar conjunctiva and extraocular muscle at 15 minutes after administration.
2) In rabbits, TA-058 was injected intramuscularly at the dosis of 50 mg/kg. The concentration of TA-058 in aqueous humor at 1 hour after administration was 2.4 μg/ml and the ratio of concentration (aqueous humor/plasma) was 6.0 percent.
TA-058 showed very good penetration into ocular tissues, especially lid, bulbar conjunctiva and extraocular muscle at 1 hour after administration.
3) TA-058 was administered by intravenous infusion to 4 cases of ulcus cornea, 1 case of traumatic iridocyclitis and 1 case of panophthalmitis.
In 2 cases out of totally 6 cases, good clinical results were obtained.
4) No side effects nor abnormalities in laboratory findings were noted.

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