A double-blind controlled study on scarlet fever patients treated with talampicillin was done in comparison with ampicillin, and following results were obtained.
1. Total of 324 scarlet fever patients were treated with the dose of 720 mg/ day of ampicillin (ABPC group), equivalent dose of talampicillin (TAPC-A group) or half dose of it (TAPC-B group) for 7 days.
2. Four cases who could not take the capsule were excepted as dropout cases, and finally 107 cases of TAPC-A group, 105 cases of TAPC-B group and 108 cases of ABPC group were analyzed.
3. There were no significant differences in all background factors between each group.
4. Minimum inhibitory concentrations of ABPC were examined on 69 strains out of isolated Streptococci, and all of them were shown less than 0.1 μg/ml.
5. Overall clinical improvements between each group were compared on total or classified cases according to every background factors. Only on 20 kg or more body weight cases, ABPC group were superior to TAPC-B group, and there were no differences between each group under other analyses.
6. In most cases, pharyngeal pathogens disappeared within 24 hours after initiation of medication, and the cases who were decreased on the pharyngeal pathogens were apparently less in number in ABPC group and slightly less in TAPC-B group than that in TAPC-A group.
7. Pathogens discharging cases after final medication, were observed more in number in TAPC-B group than ABPC group.
8. Daily improvements of body temperature and exanthema were not significant in difference between each group.
9. Skin rash, gastric disturbance and diarrhea and/or loose stool were observed as side effects, and these were found somewhat frequently in ABPC group, but it was not significant statistically.
10. Various biological examinations were studied before and after the treatment, and no abnormal values caused by medications were noted on cases of all groups studied.

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Clinical usefulness of talampicillin (TAPC) was investigated in comparison with ampicillin (ABPC) under the double-blind test on patients with urinary tract infections, and following results were obtained.
1. Following 3 groups were categorized according to medication: TAPC 1g/day dosed group, TAPC 0.5g/day dosed group and ABPC 1g/day dosed group. All cases were medicated for 3 days.
2. Twenty-seven out of 226 cases were decided as dropout cases, and 199 cases were analyzed for evaluation of effectiveness.
3. Clinical improvements were observed in 87.9% on TAPC 1g group, 84.8% on TAPC 0.5g group and 83.6% on ABPC 1g group, respectively. There was no significant difference between each group statistically.
4. Significant correlations were observed between sensitivity to ABPC of urinary isolates and clinical improvements, and overall improvement of TAPC lg group was superior to TAPC 0.5g group, under examination with analysis of variance.
5. Under analysis of above method, between bacteriological improvement of urine and sensitivity to ABPC of isolated pathogens, significant correlations were found, and bacteriological improvement of TAPC 1g group in all pathogens isolated cases was superior to that of ABPC 1g group and to that of other two groups in E. coli isolated cases.
6. There were no differences in improvements of other clinical symptoms between each group.
7. Most of urinary isolates were E. coli (72.0%), and substituted infections were observed slightly more in TAPC 0.5g group, but differences between each group were not significant.
8. Gastrointestinal disturbance and skin rash were observed in 17 out of 214 cases, and no differences were found between each group, statistically.
9. From the results of this investigation, it is concluded that talampicillin is excellently effective for simple acute urinary tract infections, and its clinical and bacteriological value is identical with or rather better than equivalent dose of ampicillin.

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Absorption and excretion were investigated with healthy male volunteers dosed preprandial and post-prandial 3 times a day with equimolar dose of ampicillin and talampicillin.
The results were shown that drug absorption was influenced by meal even on the groups of pre-prandial administration, and on post-prandial administered groups, the influences were more remarkable.
On post-prandial administered cases, absorption of drug was prolonged and the peakof blood concentrations were lowered dose by dose.
Blood concentrations after each medication of talampicillin were kept higher than twice or more that of ampicillin.
Total urinary excretion rate after administration of talampicillin t. i. d. was shown about twice compaired with ampicillin medicated cases of either pre- or post-prandial administrations.
Urinary concentration through night was highest in talampicillin post-prandial medicated group in comparison with other groups.

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The MICs of talampicillin against Staphylococcus aureus, Escherichia coli, Klebsiellaand Pseudomonas aeruginosa were similar to those of ampicillin.
To evaluate the clinical effect of talampicillin, the treatment with the drug was made in 36 patients of infections including 24 of respiratory infections, 11 of urinary tract infections and one of biliary infection. One patient was cured with excellent clinical effect, 24 were good, 3 were fair, 3 were failure and 5 were undetermined.
As to the side effects of the drug, nausea and discomfort of the epigastrium were noticed in one patient and rash in one patient, respectively, during the treatment.

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Total of 20 patients suffering from respiratory infections were treated with talampicillin.
These were included 8 cases of acute bronchitis, 7 of acute broncho-pneumonia and acute pneumonia, 2 of chronic bronchitis and each one of bronchiectasis, pleurisy and pulmonary abscess.
Excellent clinical improvements were observed in 3 patients (15%), good in 11 (55%) and moderate in 6 (30%).
Side effect was noted as skin rash only in 1 case, and no other complaint such as gastric disturbance was encountered.
The frequency of side effect following the medication of talampicillin seems to be less than that of ampicillin.

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Talampicillin, phthalidyl ester of ampicillin, is a new antibiotic. Laboratory and clinical studies on talampicillin were performed with the following results.
1. Susceptibility:
Talampicillin showed MIC values of ≤ 0.2-3.13 μg/ml against 52 strains of Hemophilus influenzae isolated from the sputum.
2. Tissue distribution in rats:
After oral administration of talampicillin, 100mg/kg, the concentration levels were measured highest in the liver, followed by the serum, the kidney and the lung in that order. They all attained the peak at 1 hour after the administration and half-life was 1 hour.
3. Clinical application:
Talampicillin was administered orally to 32 patients (23 cases of respiratory infections, 9 of urinary infections) at a daily dose of 0.5-1.5g. Talampicillin was remarkably or moderately effective in 24 patients (15 (65%) of respiratory infections, 9 (100%) of urinary infections).
4. Adverse reactions:
Side effects were observed in 2 cases loose stool in one case, loose stool and eruption in the other. Each cases were restored to normal by cessation of administration.

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From the studies on the metabolism of a new antibiotic, talampicillin, it was shown that talampicillin was hydrolyzed somewhat more rapidly than pivampicillin by the organ homogenates of rats. In comparison with those of four animal species, the speed of hydrolyzation of dog was the slowest in the experiment using intestinal homogenate, but there found no marked difference in the case of liver homogenate.
Clinically 4 patients with tonsillitis, 2 with bronchitis, 1 with pneumonia and 1 with cystitis were treated with talampicillin. Except for the case of pneumonia, all cases were evaluated good or fair concerning the clinical effect. The case of pneumonia showed transient eruption 8 days after the cessation of talampicillin dosing.

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Talampicillin, phthalidyl ester of Ampicillin was given in five male volunteers to study the serum concentrations and urinary excretion and the results were compared to those of Ampicillin.
Peak concentrations in the serum were obtained at 1 hour after oral administration of 250 mg of Talampicillin, ranging 0.7-2.4 μg/ml, and the average concentrations at 1/2, 1, 2, 4 and 6 hours after administration were 1.47, 1.57, 0.96, 0.48, 0 μg/ml. In contrast to this, peak concentrations obtained at 1 hour after administration of Ampicillin ranged 0.4-0.9μg/ml, and the average concentrations at 1/2-6 hours were 0.2, 0.7, 0.63, 0.41, 0μg/ml, indicating the ester was absorbed more rapidly and more completely than the parent compound. Average urinary recoveries within 6 hours ranged from 34.4 to 68.4%(average 47.0%) with Talampicillin compared with 25.6 to 47.8%(average 35.2%) with Ampicillin.
Eleven cases of various respiratory infections (including 2 cases of pneumonia and 3cases of middle lobe syndrome) and 2 cases of urinary tract infections were treated with 750-2, 000 mg of Talampicillin divided into 3-4 times daily, for 3-31 days. Seven cases responded satisfactory. Out of 6 cases in which causative organisms, including Diplococcus pmeumoniae, Staphylococcus aureus, Haemophilus influenzae were isolated, 4 cases responded well clinically as well as bacteriologically.
No remarkable side effect was noted except stomach ache in one case and skin rash in another, appearing after one day administration in each.

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Clinical experiments were performed with talampicillin hydrochloride and the following results were obtained.
1. 0.5-1.0g of talampicillin hydrochloride as daily dose in 4 times was given to the total of 87 patients including 8 bacterial pneumonia, 62 acute bronchitis, 4 pharyngo-laryngitis, 2 acute tonsillitis, 2 chronic bronchitis, 4 acute enteritis and 5 pyelonephritis. Sixty-four out of 87 patients were effective and the clinical effective rate was 75.8%.
2. Side effects were observed in 21 cases (24 occasions) out of 121 cases administered talampicillin hydrochloride. The complaints and the number of occasions were as follows, gastro-intestinal disturbances 10 occasions, rash 8, headache 3, vertigo 2, itchihg 1. Most of these were mild.
3. Before and after the treatment with talampicillin hydrochloride, examinations of peripheral blood picture (Hb in 46 cases, RBC in 44, WBC in 42), liver function tests (SGOT and S-GPT in 37 cases) and renal function test (S-creatinine in 36 cases) were performed. Slight decrease in Hb and RBC was noted in one case. S-GOT and S-GPT values increased up to 55-60 units, 48-95 units in each three cases. There were no abnormal changes in renal function test.

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Talampicillin, 0.5-1.5g daily, was used orally for 3-30 days in 18 patients of various infectious diseases (bronchitis 6, pneumonia 3, pulmonary abscess 1, bronchiectasis 1, tonsillitis 3, cystitis 1, pyelonephritis 1, cholecystitis 2).
Eight of them had severe underlying diseases (chronic renal insufficiency 2, gastric cancer 2, rheumatoid arthritis 1, cerebral hemorrhage 1, cholelithiasis 2).
1. The clinical results were good in 14 patients, fair in 3 patients and poor in only one patient.
2. Side effects were observed in 3 patients (eruption 1, mild anorexia 1, severe anorexia 1).
3. Serum concentrations of Talampicillin were examined in 5 patients at 1, 2, 3-3.5 and 6 hours following initial oral administration of 250 mg of the drug after meal. Mean levels were 0.55, 0.88, 0.85 and 0.19 μg/ml, respectively. It might be due to post prandial administration and to severe underlying diseases that these serum levels were low, and that variety in the levels was seen in each case.

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Phthalidyl D-α-aminobenzylpenicillinate hydrochloride (Talampicillin), a newly developed Ampicillin derivative, was examined on its antibacterial activity and absorption after per os administration. Some clinical trials were also carried out.
1. Tests on the sensitivity of the clinical isolates revealed that the sensitivity of Staphylococcus aureus and E. coli strains to TAPC was similar to that of ABPC.
2. Blood levels of TAPC in human adults administered with 250 or 125mg showed a peak (4.4, 2.3 μg/ml) 1 hour after per os.
3. Seven patients with various infections (respiratory tract and urinary tract) were treated with TAPC (0.5-0.75g). Favourable results were obtained in five of the cases. Eruption and nausea were observed in each one patient.

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Antibacterial activity, absorption, excretion and clinical efficiency on a new ampicillin derivative, talampicillin hydrochloride (TAPC), were studied and the following results were obtained.
1. The minimal inhibitory concentrations (MIC) of TAPC against clinical isolates were determined.
The MIC against 43 strains of Staphytococcus aureus were 0.39 μg/ml or less in 5 strains, 1.56-6.25 μg/ ml in 17 strains, 12.5-50 μg/ ml in 14 strains and 100 μg/ ml or more in 7 strains. The MIC against 36 strains of E. coli were 12.5-50 μg/ml in 16 strains and 100 μg/ml or more in 20 strains. The MIC against 17 strains of Klebsiella were 50 μg/ml in only 1 strain and more than 100 μg/ ml in the other strains. The antibacterial activity in vitro of TAPC was equivalent to or less than that of ampicillin.
2. TAPC produced peak serum ampicillin level of 4.9-9.0 μg/ ml at 1 to 2 hours after oral administration of 250mg to healthy adult subjects. The average urinary recovery rate in 6 hours was 62.5%.
3. Daily dose of 0.5 to 2g of TAPC were given orally to total 14 patients of 7 cases with respiratory infection and 7 cases with urinary tract infection. The clinical results were 6 excellent, 4 good, 1 fair and 3 poor. In 3 of 14 cases slight nausea was noted. Any other side effects were not observed.

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Fundamental and clinical studies on a new ampicillin derivative, talampicillin hydrochloride (TAPC) were carried out and the results were as follows.
1. Absorption and excretion:
In 3 healthy adults, the peak blood levels were shown 3.7-5.1 μg/ml and 12.5 μg/ml at 1-2 hours after single oral administration of 250 mg and 500 mg of TAPC respectively, and the half life time of blood levels were about 70-80 minutes.
Urinary recovery rate during 4 hours was shown more than 50 percent and 53.8-60.5 percent were excreted in 6 hours.
2. Distribution to organs in rats:
The concentrations in organs of rats administered the dose of 20 mg/kg orally were the highest in liver, followed by kidney, serum and lung in order.
3. Clinical study:
Out of fifteen patients with respiratory infections treated with TAPC 1 to 2g daily, 7 cases were improved and in 5 cases out of 7 chronic bronchitis with Hemophilus influenzae the organisms were cleared.
4. Side effects:
Only one out of 15 cases developed skin rash.
No other objective and subjective side effect was noted and no abnormal value was seen in hematological, biochemical and urinary examinations during this study.

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Talampicillin, a new broad-spectrum semisynthetic penicillin for oral use was studied both fundamentally and clinically. Results were summarized as follows.
1. Urinary concentration and recovery after oral administration of 250mg of Talampicillin were about twice higher than those of 250mg of Ampicillin.
2. Thirty cases of urinary tract infections were treated with Talampicillin at a daily dose of 750mg. Satisfactory results were obtained in 21 cases (81% in 16 cases of acute simple cystitis and 57% in 14 cases of chronic complicated urinary tract infections).
3. Subjective side effect was not seen.
4. It was considered that the daily dose of 750mg of Talampicillin was sufficient for the treatment of acute urinary tract infections, but for the chronic urinary tract infections, further investigations should be carried out hereafter.

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1. Antibacterial Activity
Antibacterial activities of talampicillin against clinical isolates of E. coli and Serratia were similar to or less than those of ampicillin.
2. Blood level
A single oral dose of 250mg of talampicillin in fasting state produced a peak level of 4.3μg/ml at 1-hr after administration and showed a level of 0.2μg/ml even at 6-hr.
3. Urinary excretion
A single oral dose of 250mg of talampicillin produced an average urinary excretion rate of 42.5% in the first 6-hr period after administration.
4. Clinical efficiency
Use of talampicillin for 26 patients with infections in urinary tract or genital organs gave the results of 15 excellent cases, 6 good and 5 poor. The effective rate was 80.8%.
5. Side effect
In 2 of 26 cases nausea was noted and in one case of them the medication was discontinued because of it.

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In two cases with normal renal function, the blood levels reached the maximum (4.3μg/ml, 4.5μg/ml) at 1-2 hours after administration of Talampicillin 500 mg per os. In three cases with impaired renal function, the blood levels reached the maximum (7.6μg/ml-9.0μg/ml) at 2-4 hours after administration of Talampicillin 500 mg per os at fasting time.
The urinary recovery were 146.8 mg and 144.8 mg during 6 hours after administration of Talampicillin 500 mg per os in two cases with normal renal function.
Sixty-two cases with lower urinary tract infections were treated with Talampicillin 750 mg per day per os. Excellent or good results were obtained in 42 cases. Side effects were observed in 9 cases of this series 4 were gastro-intestinal symptoms and 5 were skin eruption. Talampicillin administration was discontinued in 2 cases of them.

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Fundamental and clinical studies on Talampicillin were performed and the following results were obtained.
1) Antibacterial spectrum: Antibacterial spectrum of Talampicillin was the same as that of Ampicillin.
2) Susceptibility of clinical isolates: Talampicillin showed similar antibacterial activity to Ampicillin against Staphylococcus aureus and E. coli, but both antibiotics were inactive against Klebsiella pneumoniae and Pseudomonas aeruginosa.
3) Concentrations in the blood and urine: Concentrations in the blood and urine of three healthy volunteers taking Talampicillin 500 mg were determined by the cylinder plate method using PBS as standard.
The peak concentration in the blood was observed 1-hr after administration at an average level of 9.6μg/ml. The urinary concentration reached a peak after 2-hrs. at an average of 1183.3μg/ ml. The urinary recovery rate in the 6-hrs. period was 71.9%.
4) Tissue concentration: Tissue concentrations in groups of rats each consisting of three SD rats were found highest in the liver, followed by the kidney, serum, heart, lung and spleen, in that order. But only a trace of the drug was observed in muscle.
5) In vivo metabolism: Metabolism of Talampicillin was studied on urine of human receiving Talampicillin by bioautogram prepared with TLC. It was found that Talampicillin was metabolized into Ampicillin and then excreted in the urine.
6) Talampicillin was given to 16 patients with surgical infectious diseases and the following results were obtained good in 10, poor in 5, unknown in 1. The effective rate was 66.7%.
Vertigo and itching were noted in one of these cases. But no other side effect was observed.

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The fundamental and clinical studies on Talampicillin hydrochloride (TAPC) in the surgical field were performed, and the following results were obtained.
Blood levels and urinary excretions were measured in 3 healthy adults administered single oral dose of 250 mg of TAPC early in the morning at fasting.
The maximum blood level on the average was achieved 1 hour after administration, and average concentrations were shown 3.8μg/ml at 30 minutes, 4.5μg/ ml at 1 hour and 1.4μg/ml at 2 hours following the initiation.
Urinary recovery rate within 6 hours was 55.1% of an administered dosage on the average.
Eleven cases suffering from acute suppurative infections of soft tissue in surgical field were treated with TAPC.
Excellent improvements were obtained in 3 cases, good in 4 and moderate in 3. No change was observed only in one case.
The effective rate including excellent, good and moderate cases resulted in 90.9%.
The side effect was noted in one case as extensive skin rash.
No other side effect such as gastrointestinal disturbance was observed in this investigation.

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Talampicillin (TAPC), a new antibiotic derived from ampicillin, has a broad spectrum and a bactericidal action. The authors investigated serum levels, urinary excretion, clinical effectiveness and untoward side effects of the agent. The results obtained are summarized as follows:
1. Following an oral administration of 250 mg Ampicillin and same dose Talampicillin in 3 healthy adult volunteers by crossover method, the mean serum levels of Talampicillin showed a peak of 2.66μg/ ml, 4 times as much as that of Ampicillin at 1-2 hours after administration, with 96.87 mg (38.7%) urinary excretion of Talampicillin within 6 hours.
2. Talampicillin was given on 37 patients with infections in the field of surgery, and the result was excellent in 12 cases, good 9, fair 11 and poor 5, the effectiveness rate accounting for 86.5%.
Nausea was observed in 2 cases and eruption in one case among 37 patients in trial.

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Talampicillin is a new penicillin with a broad-spectrum and is better absorbed than ampicillin after oral administration. Studies on talampicillin in the field of pediatrics were performed and the following results were obtained.
1. Blood concentrations after oral administration of talampicillin to six adult volunteers were compared with those obtained with equivalent dose of ampicillin in a crossover study. At 0.5-2 hours after oral administration, talampicillin produced obviously higher average blood concentrations than those of ampicillin.
2. Blood concentrations of seven infants after a single oral administration of talampicillin 125 mg were 5.46-9.31μg/ ml at 1st hour, 2.37-2.7μg/ml at 3rd hour and 0.34-0.62μg/ml at 6th hour. These values were slightly superior to those of amoxycillin and pivampicillin obtained in other experiments.
3. Blood concentrations were elevated in proportion to increase of dose.
4. Urinary excretion rates for 6 hours after oral administration of talampicillin tosix adult volunteers were 66.6-99%.
5. 20-30mg/kg daily dose of talampicillin was given to patients with acute tonsillitis, lacunar tonsillitis, acute bronchitis, scarlet fever, etc. and 30-40mg/kg to patients with bronchial pneumonia. Most of these patients showed good response to the treatment with talampicillin and the effective rate in 34 subjected cases was about 90%.
6. Clinical laboratory tests (GOT, GPT, BUN, etc.) were conducted on some patients including one case treated for a period of 100 days at 20mg/kg daily dose of talampicillin. No abnormal values were observed.
7. Anorexia was noted in one case who was able to continue the talampicillin therapy. Other side effects were not observed.

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Fundamental and clinical studies on Talampicillin were carried out and the following results were obtained.
1. The minimal inhibitory concentrations of Talampicillin against clinical isolates of E. coli and Staphylococcus aureus were similar to those of Ampicillin.
2. It was found that Talampicillin was well absorbed by oral administration and then was measurable in umbilical cord blood and amniotic fluid.
3. Talampicillin was given to 16 patients with infection of urinary tract and sexual organ and the effective rate of 68.8% was obtained.
4. No remarkable side effect was observed.

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Absorption, antibacterial activity and clinical effects were studied on talampicillin to evaluate its clinical usefulness, and the results were as follows.
1. Concentrations of ampicillin in the serum of 5 healthy volunteers reached a peak of 4.1μg/ ml at 1 hour after the oral administration of talampicillin 250 mg. These values were approximately twice as high as those of ampicillin observed in the crossover test on the equivalent dose and were similar to those of amoxycillin.
2. In maternal-fetal transfer in pregnant rats, the concentrations in most of organs of fetuses were shown 1/3-1/5 in comparison with those of mothers.
3. The minimum inhibitory concentrations (MIC) of talampicillin in clinical isolates of various bacterias were measured. The mode of distribution of the MIC was similar to those of ampicillin and its analogues. The MIC in majority of the isolates were distributed as follows.
Streptococcus pyogenes:≤ 0.1μg/ml
Indol negative Proteus species: 1.56-3.13μg/ ml
E. coli: 3.13-12.5μg/ml
4. There was a correlation between the antibacterial activity of talampicillin and ampicillin on Staphylococcus aureus and E. coli.
5. Talampicillin of 0.5-1.0g daily was administered for 3-7 days to 12 patients with various infections in the field of gynecology and obstetrics, and the effective rate was 75%. In two cases, mild gastric disorders were recorded as side effect.
No significant changes due to talampicillin were found in the laboratory tests carried out before and after the administration.

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1. MIC against 20 strains of Staphylococcus aureus isolated from various lesions of skin infection was 0.1μg/ ml in 2 strains, 0.2μg/ml in 1 strain, 0.8μg/ ml in 1 strain, 1.6μg/ml in 2 strains, 3.2μg/ml in 2 strains, 6.3μg/ml in 4 strains, 12.5μg/ml in 3 strains, 50μg/ml in 2 strains and>100μg/ml in 3 strains.
2. Skin and serum concentrations of Talampicillin were studied in rats and compared with those of ABPC. The formers were about four times higher than the latters. In both drugs the skin concentrations were about 1/4 of the serum concentrations.
3. Clinical use of Talampicillin showed the following results: excellent in 3 cases, good in 4 cases, fair in a case and failure in a case. In a case the patient complained of nausea and diarrhea, and could not continue to take the drug.

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The laboratory and clinical experiments were performed on Talampicillin (TAPC) in ophthalmological field, and results obtained were as follows.
1. TAPC showed a broad antimicrobial spectrum resembling that of Ampicillin (ABP C) and revealed wide ranging antibacterial activity against gram positive and negative bacteria causing ocular infections.
2. The sensitivity for Staph. aureus was distributed in the range of ≤ 0.19-> 100μg/ml with peak at 12.5μg/ml in 25% of the strains.
3. Blood concentration of TAPC following an oral administration of 250mg to healthy adults, reached its peak level (7.0μg/ ml) after one hour, and gradually decreased to 0.79μg/ml after 6 hours.
A crossover study was performed with ABPC, and the peak level of TAPC was about3 times higher than that with ABPC.
4. After an oral application of 50mg/kg in rabbits, the aqueous levels were observed from 1 hour to 6 hours, and the peak level was obtained after 1 hour (2.12μg/ml). Aqueous/Serum ratio was 11.73-31.25%.
Ocular tissue concentrations were tested at one hour after oral administration of TAPC. TAPC was well transferable to both the outer and inner parts of the eye.
5. Oral administration of 125-250mg TAPC 4 times daily revealed good therapeutic effects in 21 cases out of 24 cases of ocular infections, such as hordeolum, lid abscess, dacryocystitis, corneal infiltration, corneal ulcer and orbital phlegmone.
6. As side effects, anorexia was experienced in 2 cases, but no other severe ones were noticed.

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Fundamental and clinical evaluations of a new semisynthetic penicillin, talampicillin, were performed. The results obtained were as follows.
1. In vitro antibacterial activity: The minimal inhibitory concentration (MIC) of talampicillin was measured by an agar plate dilution method using heart infusion agar (Eiken). Talampicillin revealed an excellent, broad spectrum antibacterial activity against gram positive and gram negative species of 23 standard test organisms of various bacteria. The antibacterial spectrum of talampicillin was the same as that of ampicillin.
2. Concentration in blood: The level of blood concentration after giving 500mg of oral talampicillin was determined in 3 cases of healthy adult. The maximal level measured 11.5μg/ml one hour after oral administration. Even 6 hours after oral administration, clinically effective serum talampicillin concentration 2.0μg/ml was still demonstrable.
3. Concentration in tissues: One hour after a single oral dose of 500 mg, the concentration in the tissues of palatine tonsilla was 1.2μg/g as against 10.7μg/ ml in the serum, and the concentration in the tissues of mucous membrane of maxillary sinus was 0.8μg/g when measured 11.1μg/ in the serum.
4. Results of clinical treatment: Talampicillin of oral administration was tested in 32 cases of usually encountered acute infections in the otorhinolaryngologic field, the results being excellent in 13 cases, good in 14 cases, fair in 3 cases and poor in 2 cases. When the excellent and good were bracketed together, it amounts to 27 cases (84%). It can be considered as high effective ratio.
5. Side effect: No side effect was shown with the oral administration of talampicillin. The comparative examination of hepatic function, electrolyte and auditory acuity before and after oral administration showed no significant disturbance.

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The fundamental and clinical studies were carried out on Talampicillin (TAPC), and the following results were obtained.
1. The growth of Staphylococcus aureus 209P was completely inhibited by 10 fold dilution of serum obtained at 1, 2, 3 and 4 hours after oral administration of TAPC 250 mg.
2. Serum concentration was determined by thin-layer cup method with Bacillus subtilis ATCC 6633 as the test organism. The peak serum level was obtained at 1 hour after a single oral administration of TAPC, and the level was still measurable at 6 hours after the administration.
3. The concentrations in palatine tonsilla and maxillar-membrane after 2 hours of oral administration of TAPC were measured and compared with the corresponding serum levels.
4. TAPC was administered orally to 35 cases of various infections in otorhinolarygological field, and clinical results were excellent in 17 cases (48.6%), good in 14 cases (40.0%) and poor in 4 cases (5.7%).
5. Side effects were obtained in 2 out of 35 cases; nausea in one and gastro-intestinal disturbance in the other. The medication was discontinued in these cases.

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Clinical investigation was made on the effect of talampicillin hydrochloride in otorhino-laryngological infections. This antibiotic was administrated orally at the dosage of 500 mg/day to adult patients. Excellent and good results were observed in 81% among 21 patients with suppurative otitis media, furuncle of the external ear, furuncle of the nose or acute tonsillitis. One patient complained of epigastric distress as side effect.

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Talampicillin is a derivative of Ampicillin. It was confirmed that this derivative is absorbed like Ampicillin after oral administration and is measured at higher blood level comparing with Ampicillin. The authors have studied the drug concentration of oral tissues in Wistar rats such as gingiva, tongue, dental pulp, submaxillary lymphonodi, submaxillary glands and parotid glands and compared it with serum level.
The concentration was measured by double layer method, using Streptococcus pyogenes Cook.
The results were estimated that the serum concentration was rapidly reached to the maximum level in half an hour after the initiation of the medication. The maximum serum level was as 6 times, and tissues concentrations were approximately as twice as that of Ampicillin after oral administration of equivalent dose. Thirty-six patients were treated with Talampicillin, and good improvements observed in 27 cases. Side effects such as diarrhea or exanthema were appeared in 4 patients out of 36.

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Having studied clinical effects of talampicillin, we obtained the following results
1) The blood level got to the maximum concentration (3.7μg/ ml) after 2 hours of 250 mg talampicillin administration.
2) The antibacterial effect of talampicillin against Streptococcus or Staphylococcus was stronger than the other antibiotics.
3) Effectiveness of talampicillin on 50 patients in oral surgery was about 70.0%.
4) No prominent side effect was observed in the patients treated with talampicillin.

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Bacteriological evaluations on Talampicillin were performed comparing with Ampicillin and the results were obtained as follows.
1. The antibacterial spectrum of Talampicillin against gram positive and gram negative bacteria was similar to that of Ampicillin. In the level of activity, however, Ampicillin was slightly more effective than Talampicillin.
2. In sensitivity test on clinical isolates, the distribution was found to be extended between sensitive and high resistant strains in isolates of Staphylococcus aureus, and to have the peak at 12.5μg/ml and>100μg/ ml in E. coli and 6.25μg/ ml in Proteus group. Ampicillin-resistant strains were also resistant to Talampicillin.
3. Talampicillin was inactivated by β-lactamase extracted from somatic material of E. coli.
4. On the antibacterial activity determined by the nephelometry method, Talampicillin showed more rapid bacteriolytic activity than that of Ampicillin in Staphylococcus aureus, but in E. coli the result was quite reverse.
5. On the protecting effects for mice experimental infections, the effect of Talampicillin was similar to that of Ampicillin for Staphylococcal infection and was superior to Ampicillin for E. coli and Klebsiella pneumoniae infection. But both drugs were not effective for infection by Ampicillin resistant strain of E. coli.

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The pharmacological actions of talampicillin (TAPC) which is a phthalidyl derivative of ampicillin were investigated.
Summary of pharmacological actions and minimal effective doses (MED) of TAPC was as follows: fall of blood pressure of the rabbit (2 mg/kg), short breathing of the rabbit (5 mg/kg), bradycardia on ECG of the nonanesthetic rabbit (10 mg/kg), inhibition on isolated guinea pig atrium (5× 10^-5 g/ml), constriction of isolated rabbit ear vessels (2× 10^-3 g/ml), stimulation on permeability of rabbit abdominal skin vessels (100 p, g), inhibition on isolated rabbit intestine (2× 10^-5 g/ml), and inhibition on isolated rat uterus (5× 10^-4 g/ml for nonpregnant uterus and 2× 10^-5 g/ml for pregnant uterus). No effect on isolated guinea pig intestine and trachea was observed in concentrations up to 10^-3 g/ ml.
The pharmacological actions of its metabolites (PAA, HTA and PL) were partly identical to those of TAPC and their MED were much less than those of TAPC. MED of TAPC were much larger than minimal inhibitory concentrations and maximal blood levels in clinical uses.
The increase in body weight, urinary excretion of potassium and urinary findings in the rat applied with TAPC in doses from 25 to 100 mg/kg orally once a day for 7 days were similar to normal values and those of control group. Increased urinary volume and decreased urinary excretion of sodium were observed in proportion to the increase in the doses applied. However, those were restored after cessation of the drug administration.

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Antibacterial activities of a new orally active ampicillin ester, talampicillin hydrochloride (TAPC), were compared with those of ampicillin (ABPC). TAPC showed a broad-spectrum antibacterial activity against Gram positives and negatives as seen in ABPC. Sensitivity distributions in clinical isolates of Staphylococcus aureus, Streptococcus pyogenes, Streptococcus faecalis, Escherichia coil and Proteus were similar between TAPC and ABPC, but TAPC was rather weaker in the activity than ABPC by one test tube in a twofold dilution scale. Turbidimetric and viable bacteria studies using a biophotorecorder revealed that the inhibitory activity of TAPC appeared after some lapse of time. Thus it was suggested that TAPC exhibited the activity of ABPC itself after it was hydrolyzed to ABPC and phthalidyl moiety.
In experimental murine infections with Staphylococcus aureus, Streptococcus pyogenes, Streptococcus pneumoniae, Escherichia coli and Proteus mirabilis, TAPC showed about twice as potent protective activities as ABPC. TAPC was not effective against murine infections with penicillin-resistant E. coli and Pseudomonas aeruginosa.

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Absorption and urinary excretion of a new ampicillin derivative, talampicillin hydrochloride, were studied.
The peak concentrations of ampicillin in plasma of mice and rats after oral administration of talampicillin hydrochloride were much higher than those after ampicillin administration. A peak in plasma concentration was observed 15 minutes after administration of talampicillin hydrochloride in mice and 30 minutes in rats, whereas the concentration reached a peak 30 minutes after ampicillin administration in both species. An average area under the plasma concentration curves for talampicillin hydrochloride was approximately 5 times greater than that for ampicillin in mice and was 3 times greater in rats, indicating better absorption of talampicillin hydrochloride in both animals.
Talampicillin hydrochloride or ampicillin with 125 mg and 250 mg was orally given to fasting volunteers. The absorption of talampicillin hydrochloride was twice as better as that of ampicillin. Approximately 50% of the given amount of talampicillin hydrochloride was recovered in the urine, whereas 30% was recovered when ampicillin was given.
To determine the effect of food on the oral absorption of talampicillin hydrochloride, 10 subjects received 250 mg doses in fasting and then post-prandial state with one week interval. Neither the peak plasma concentration nor the total amount of urinary excretion during 6 hours was influenced by food. But the peak plasma concentration was seen 1 hour after when talampicillin hydrochloride was given in fasting state, in contrast to 2 hours when given in post-prandial state. The majority of ampicillin in urine was excreted during the first 2 hours in fasting state, in contrast to 2 to 4 hours in post-prandial state.

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Distribution and excretion of the phthalidyl moiety of talampicillin hydrochloride were studied in rats after oral administration of phthalidyl-labelled ¹⁴C-talampicillin hydrochloride (¹⁴C-TAPC).
1. The blood concentration of radioactivity reached a peak at 1 hr after and then declined with a half-life of about 5 hr.
2. The tissue concentration of radioactivity reached a peak at 1 hr after. At this time, radioactivity was highest in plasma, followed by that in kidney, liver, spleen, lung, heart and brain in this order. Thereafter, the radioactivity declined in parallel with plasma levels.
3. The radioactivity excreted in urine and feces amounted to 89.0% and 5.4%, respectively, within 48 hr.
4. Biliary excretion of administered radioactivity was 2.3% within 48 hr.
These results suggest that the phthalidyl moiety of TAPC is excreted rapidly into urine.

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The acute toxicity of talampicillin hydrochloride (TAPC), a new orally active ampicillin derivative, was studied in Sprague-Dawley rats and ICR mice. The drug was administered as a single dose in three different routes, orally, subcutaneously and intravenously.
Reduced spontaneous locomotor activity was a common symptom in all three routes. Soft feces by the oral route, dyspnoea and hemoglobinuria by the intravenous route were also observed. These symptoms were almost same in both species.
The lethal dose was in excess of 4000 mg/kg in both sexes of rats and mice when TAPC was administered orally or subcutaneously. By the intravenous route, the median lethal dose was found to be 786 and 817 mg/kg respectively in the male and female rats, while in excess of 1000 mg/kg in both sexes of mice.
Severe congestion of lungs was observed in animals dying on test. There were, however, no adverse macroscopic post-mortem findings in any animals examined at the end of the seven day observation period.

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Subacute toxicity of talampicillin hydrochloride was studied in rats. The drug was administered orally for 7 weeks at doses of 30, 100, 300 and 1000 mg/kg. In male rats dosed with 100 mg/kg and in females dosed with 100 and 1000 mg/kg of the drug, food consumption decreased slightly during the first week of administration but this had no effect on the growth rate. At 300 and 1000 mg/kg, soft feces was noted during administration and enlargement of caecum was observed at autopsy. At 100 mg/kg and over, serum total protein increased slightly in males and decreased slightly in females. The increase of serum albumin was observed in males given over 300 mg/kg of the dose. In organ weight, the weight of kidney increased in males given 1000 mg/kg. That of thymus decreased in females given 300 mg/kg as well as that of liver in females given 100 and 1000mg/kg.
All the other parameters remained within normal limits and histopathological anomalies were not observed in any dose group.

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Chronic toxicity of talampicillin hydrochloride was studied in rats. The drug was administered orally for 26 weeks at doses of 30, 100, 300 and 1000 mg/kg.
In all animals of any dose group, food consumption decreased slightly during an early period of administration but this had no effect on the growth rate. At 300 and 1000mg/kg, soft feces was noted during administration and enlargement of caecum was observed at autopsy. Also, a slight decrease was observed in serum urea nitrogen and serum GPT in males, and in serum alkaline phosphatase, serum GOT and serum GPT in females. All the other parameters remained within normal limits and histopathological anomalies were not observed in any dose group.

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The toxicity of talampicillin hydrochloride, a new orally active ampicillin derivative, was studied in beagle dogs of both sexes. The drug was orally administered to the dogs at dose levels of 0, 30, 100 and 300 mg/kg/day for five weeks.
The dogs given 30 mg/kg/day developed no clinical symptoms suggestive of drug toxicity. Most of dogs receiving 100 and 300 mg/kg/day showed vomiting during the first week, incidence of which gradually decreased, and became rare from the third week on.
No significant changes were observed in body weights, food consumption, hematological and biochemical findings and organ weights.
No pathological changes due to drug action were detected by macroscopic and histological examinations.

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Teratological effects of a new ampicillin derivative, talampicillin hydrochloride (TAPC), were studied in rats. TAPC was administered orally at the daily doses of 125, 250, 500 and 1000 mg/kg of body weight to pregnant rats for 7 days from 8th to 14th day of gestation. The results obtained are summarized as follows:
1. Effects in dams All dams survived the experimental period. In 500 and 1000 mg/kg group, soft feces were observed during the period of administration and cecal enlargements were found at sacrifice on day 20 of pregnancy, but not on weaning. The food intake was decreased and the gained body weight was suppressed in treated groups as compared with the control.
2. Effects in fetuses No significant differences were observed between the control and the medicated group with regard to the litter size, embryo or fetal mortality and mean body weight. Gross, visceral, and skeletal abnormalities were observed on control and treated groups in low incidence.
3. Effects in newborns There were no significant differences between control and treated groups in postnatal development. Skeletal malformations were observed in 250 and 500 mg/kg group, but these abnormalities have been known to occur spontaneously. No abnormalities were observed in the behaviors of offspring.
The above finding indicate that, under the present experimental conditions, TAPC has effects on suppression in gained body weight of dams, though it has no teratogenic effects in rats.

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Talampicillin hydrochloride (TAPC) was administered orally to mice from the 7th to 13th day of gestation once a day at doses of 31, 63, 125, 250, 500 and 1000 mg/kg and its teratogenic effects on fetuses and newborns were examined.
1. At every dose, the general behavior of dams remained normal with no death during the test. However, at doses over 250 mg/kg, the increase in body weight of dams was suppressed.
2. At doses over 250 mg/kg, the body weight gain of fetuses was suppressed roughly in parallel with the dose. This was not observed at doses below 63 mg/kg, while a dose of 125 mg/kg was a critical one at which the suppression of fetal growth was observed in some but not in other experiment. Lethal action on fetuses and teratogenic effects were not observed at any dose.
3. The period of gestation, delivery and nursing were not affected at any dose. Nor was there observed any deleterious effect on the growth and development of newborns except that the female body weight of the group given 1000 mg/kg was slightly less than that of the control until 4 days after delivery.

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Behavioral observations in mice, rats, cats and dogs revealed sedation due to high doses of talampicillin hydrochloride (TAPC). Repetitive for 8 days as well as a single oral administration of TAPC caused sedation in rats. Barbital sleeping time was prolonged with 1000 mg/kg p.o. of TAPC in mice.
In EEG studies, 100 mg/kg i.v. of TAPC enhanced slow wave activity of cortical and subcortical area except for hippocampus. The threshold of arousal responses to electrical stimulation of the mesencephalic reticular formation was slightly elevated in some cats. No abnormal EEG response to sonic stimulation and calling was observed.
A dose producing convulsions in 50% of mice after intracerebral application of TAPC was almost equal to that of ampicillin, and was about 20 times that of penicillin G potassium.
In anesthetized dogs, 3 mg/kg i.v. of TAPC caused a reduction of blood pressure and an increase in heart rate. The hypotention and increases in respiratory rate and femoral blood flow were elicited by 10-100 mg/kg i.v. Heart rate tended to increase in low doses and to decrease in high doses. With a dose of 300 mg/kg i.v., two of three dogs died. When administered into duodenum, TAPC caused a reduction of blood pressure and a decrease in heart rate in a dose of 10 g/kg, and death in a dose of 30 g/kg. Intravenous injection of phthalaldehydic and α-hydroxy-o-toluic acid, metabolites of TAPC, reduced blood pressure, and increased femoral blood flow and respiratory rate in a dose range from 30 to 300 mg/kg i.v.
Antagonizing activities of TAPC (3×10^-5 -10^-4 g/ml) against several spasmogens were detected in isolated ileum of guinea-pigs. Both contractility and rhythmicity of isolated rat uterus were suppressed at 10^-7 - 10^-6 g/ml of TAPC.
No measurable effects of TAPC were obtained in the following experiments anticonvulsive tests (maximal electroshock, pentetrazol, and strychnine), tremorine induced tremor, conditioned avoidance response, analgesic activity, rectal temperature, neuromuscular function, surface anesthesia, contractility of nictitating membrane, gastrointestinal propulsion, irritation of gastric mucosa, urine excretion, eye irritancy and antigenicity.

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