A new macrolide antibiotic preparation, TMS-19-Q·O tablet, was used to investigate the efficacy in the treatment of patients with respiratory tract infection, and the results obtained were as follows:
1. Three handred and seven cases were included in this report, and overall efficacy rate was 76.2%. Especially high clinical effect (86.0%) was observed in the treatment of patients with pneumonia including mycoplasmal pneumonia.
2. Bacteriological effect was 87.5% in 51 cases identified as single infection of Gram-positive cocci and was 48.0% in 34 cases Gram-negative rods infection.
3. Side effects were observed in 11 cases (3.50%): gastrointestinal disorder in 8, eruption in 2 and other in 1.
Abnormality in laboratory tests was observed in 23 cases, hepatic disorder in 13, renal disorder in 3 and other laboratory tests in 7.
4. It was considered from the results of clinical and bacteriological efficacy in different dose study that dose of TMS-19-Q should be 600mg.

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Clinical effectiveness of TMS-19-Q, a new macrolide antibiotic, was evaluated in superficial infectious diseases classified into 6 groups at 13 departments of dermatology. The results obtained were as follows:
1. Final global improvement rating in 311 cases were excellent in 91, good in 158, fair in 45 and poor in 17 and the effective rate was 80.1%.
2. Effective rates in each group were 71.1% in 1st group (folliculitis and acne pustulosa), 78.6%. in 2nd group (furuncle, furunculosis and carbuncle), 100% in 3rd group (impetigo), 76.9% in 4th group (phlegmone, superficial lymphangitis, erysipelas and infectious paronychia), 88.7% in 5th group (inflammatory atheroma, subcutaneous abscess, hidradenitis suppurative and acne conglobata) and 77.3% in 6th group (secondary infection).
3. Dominant strains isolated were S. aureus (40.7%), S. epidermidis (26.9%) and anaerobic bacteria (20.8%). S. aureus was frequently isolated from most of all disease. On the other hand, S. epidermidis and anaerobic bacteria were isolated mainly from 1st and 5th group.
4. Optimum daily doses would be over 600mg.
5. Slight adverse reactions such as gastrointestinal disorders, eruption and malaise were observed in 12 cases.

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The clinical study for TMS-19-Q ·O tablet was performed with multicenter trial. The results obtained were as follows;
1. Final grobal improvement rating in 332 cases of otorhinolaryngological infections were excellent in 99, good in 142, fair in 40 and poor in 51 and the effective rate was 72.6%. Those of 266 cases with acute infection were excellent in 93 and good in 121 and the effective rate was 80.5%.
2. Optimum daily doses would be 600mg based on the analysis of 144 cases of the acute infection with sensitive bacteria (MIC: ≤3.13μg/ml).
3. In acute infection, major causative bacteria were Gram-positive cocci (GPC) indicating the frequency of 72.0% in total isolates and 87.5% in singly isolated cases.
In chronic infection, although GPC were also dominant, Gram-negative bacilli were observed in 31.9%.
4. Clinical and bacteriological effective rates of 160 cases of acute infection with single species were 80.6% and 90.3%, and those of 43 cases in chronic infection were 44.2% and 72.7%, respectively.
5. The resistant rates of isolates in acute infection to TMS-19-Q were 13.3% in S. aureus, 7.7% in S. epidermidis, 6.0% in S. pyogenes and 0% in S. pneumoniae. Those in chronic infection were 20.0% in S. aureus and 25.0% in S. epidermidis.
6. Slight adverse reactions, such as skin eruption or gastrointestinal disorders were observed in 14 cases and no severe one was observed.
Slight elevation of GOT, GPT, Al-P, BUN, S-Cr. or eosinophil were observed in 12 cases.
These results suggest that TMS-19-Q would be useful antibiotic for otorhinolaryngological infections.

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Multicenter clinical trial or TMS-19-Q·O tablet was performed to evaluate the usefulness in oral surgery. The results obtained were as follows:
Clinical efficacy was assessed by clinical points. The patients entered into the trial were 77 cases with periodontitis, 23 with pericoronitis, 92 with ostitis of jaw and 18 with other infections, and the each effective rates were 80.5, 60.9, 83.7 and 72.2%, respectively. Overall effective rate was 79.0%.
Isolation frequency of organisms were 33.8% in periodontitis, 34.8% in ostitis of jaw and 17.4% in pericoronitis. Bacteria isolated were aerobic organisms (63.1%) and anaerobic organisms (36.9%).
TMS-19-Q·O tablet was well tolerated, and no adverse reaction was observed.

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Mechanisms of the disulfiram-like reaction of cephem antibiotics were studied. Changes in ethanol (EtOH) and acetaldehyde (AcH) levels in the blood with EtOH loading following daily intravenous administration of cephem antibiotics were determined in rats and the followings were found:
1. The daily intravenous injection of cefazolin, cefotiam (CTM), cefsulodin, cefoxitin or ceftizoxime in no way varied the changes in the EtOH and AcH levels in the blood with EtOH loading.
2. The daily intravenous injection of cefmetazole, cefoperazone, cefamandole, latamoxef, cefmenoxime or cefotetan caused the AcH level in the blood to be elevated significantly until at least 8 hours after the EtOH loading, but was inert on the EtOH level on the blood.
3. The daily administration of 1-methyl-2-tetrazoline-5-thione (TZ), a compound having a partial structure similar to those of the cephem antibiotics elevating the AcH level in the blood on EtOH loading, was inert on the EtOH level in the blood but elevated the AcH level in the blood. The daily administration of 1-(2-dimethylaminoethyl)-2-tetrazoline-5-thione (MTZ), a compound having a partial structure similar to that of CTM, was inert either on the EtOH or AcH level in the blood.
4. The cephem antibiotics elevating the AcH level in the blood all had a (1-methy1-1H-tetrazol-5-yl) thiomethyl group in the 3 position of the aminocephalosporanic acid nucleus.
5. It was though that the disulfiram-like reaction caused by the cephem antibiotics was derived from the elevation of AcH level in the blood.
6. The disulfiram-like reaction was presumed to take place through the mechanism that the antibiotics, when injected intravenously, might be excreted into the bile to be metabolized in the intestinal tract, where they might release TZ, which in turn might inhibit aldehyde dehydrogenase.
7. The patient on treatment with or not more than 7 days after treatment with the cephem antibiotics causative of this phenomenon should refrain from the ingestion of alcohol-containing liquor.

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The clinical effectiveness in postoperative infections of sulbactam/cefoperazone (SBT/CPZ,(SBT 0.5g+CPZ 0.5g)×2/day) was compared to that of ceftizoxime (CZX, 1.0g×2/day) by a well controlled comparative study, to have the following results.
1. The overall effectiveness rate of SBT/CPZ and CZX as judged by Judgement Committee was 84.0% (63/75) and 80.6% (50/62), respectively, and the effectiveness of SBT/CPZ and CZX as assessed by the attending surgeons was 84.0% (63/75) and 71.0% (44/62), respectively. No significant difference was noted in both assessments. In a total of 36 SBT/CPZ-treated patients with intraabdominal infections, the clinical efficacy was judged by attending surgeons to be excellent in 13 patients (36.1%), and to be excellent or good in 31 (86.1%). In the 30 CZX treated patients, it was judged to be excellent in 6 patients (20.0%), and to be excellent or good in 19 (63.3%). These results presented a significant difference (P<0.05, U-test) between the 2 drug groups.
2. The final global improvement ratio judged by attending surgeons was 85.3% (64/75) for SBT/CPZ, and 79.0% (49/62) for CZX with no significant difference. In assessment of time-course improvement, the improvement ratio of SBT/CPZ on day 4 was significantly better than that of CZX (P<0.05, U-test).
3. The usefulness rate of SBT/CPZ and CZX was 84.0% (63/75) and 73.0% (46/63), respectively. There was no significant difference between the 2 drug groups.
4. To assess the bacteriological efficacy, the eradication rate of SBT/CPZ was compared to that of CZX. There was no significant difference between 85.7% (36/42) for SBT/CPZ and 73.5% (25/34) for CZX.
5. After SBT/CPZ administration, 2 patients (2.5%) complained of side effects. In the clinical labolatory tests, abnormality related to SBT/CPZ medication was observed in 6 patients (7.5%), and that related to CZX, in 5 patients (6.4%). As to the types of side effects and frequency, no significant difference was observed between SBT/CPZ and CZX.
It is concluded from the above assessments that SBT/CPZ is a useful drug in the treatment of post-operative infections.

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Cefminox (CMNX, MT-141) was evaluated for its safety and efficacy in children. Fifteen cases of bacterial infections were treated with intravenous bolus injections of 30 to 100mg/kg/day of CMNX. Each 5 cases of acute respiratory tract, urinary tract, and gastrointestinal infections were included. All the cases were cured after the CMNX therapy. No adverse reactions were encountered with the therapy.
The serum half-life was approximately 1.5 to 2 hours after intravenous bolus injection in children.
The data suggest that CMNX is a safe and effective antibiotic when used in children with susceptible bacterial infections.

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Cefminox (CMNX, MT-141) was studied both fundamentally and clinically in the field of pediatrics with following results.
1. The MIC of CMNX for Bordetella pertussis was 0.10μg/ml in inoculum size 10⁶cells/ml.
2. Following administration of 10 and 20mg/kg of CMNX as drip infusion over 1 hour, the blood levels of the drug were 49.0±18.1 and 69.1μg/ml at completion of infusion, 28.8±7.7 and 61.6μg/ml at 1.5 hours, 23.6±9.3 and 44.1±3.8μg/ml at 2 hours and 1.4±1.4 and 4.0±0.6μg/ml at 7 hours, with T1/2 of 1.03 and 1.41±0.03 hours, respectively. Within the first 7 hours after administration, 61.4±8.2 and 55.9±0.8% of the drug dosed were excreted at active form in urine.
3. In child with encephalitis, drug considered to be good as a cephem antibiotic was achieved in the cerebrospinal fluid (the ratio of the level in the cerebrospinal fluid to that in the serum was 7.3%). In addition, in the pus in empyema also high level was reached (its ratio against blood level was 53%).
4. In the treatment of 31 cases of acute infections of pediatric field including upper and lower airway infections, empyema, whooping cough, acute urinary tract infections and phlegmon, CMNX was administered intravenously either as one shot injection as drip infusion. The clinical results obtained were rated as good or more in 93% of the cases and as fair or more in 100% of the cases. The main dosage of CMNX in these cases was about 60 to 70mg/kg per day in 2 or 3 divided doses.
5. S. aureus, S. pyogenes, S. pneumoniae, H. influenzae and ABPC resistant strain of E. coli demonstrated in various materials could be eradicated after intravenous injection of CMNX.
6. CMNX was administrated for a period of 2 to 16 days to a total amount of 1.5 to 26.5g. In none of these cases side effects developed nor any abnormality was revealed by hematological findings or results of renal or liver function.

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Fundamental and clinical trials were carried out with cefminox (CMNX, MT-141) in pediatric infections. Results were as follows.
1. The mean serum concentrations of CMNX following intravenous injection of 10, 20 and 40mg/kg were 73.1, 112.5 and 181.4μg/ml at 15 minutes after injection, respectively. The serum half-life times were 1.37, 1.20 and 1.53 hours, respectively.
Average recovery rates in the urine until 6 hours from the start of injection were 91.4, 59.4 and 85.8%, respectively.
2. The antimicrobial activity of CMNX against clinically isolated organisms was measured; CMNX was more active than CMZ and CEZ against H. influenzae. CMNX was equal to or more active than CMZ and CEZ against E. coli.
3. CMNX was administered clinically to 32 pediatric patients with various infections; 19-pneumonia, 5-bronchopneumonia, 3-bronchitis and 5-pyelonephritis.
Overall efficacy rate was 93.8%.
4. Slight elevation of S-GOT and S-GPT was observed in 2 patients. No other serious side effect was observed.

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A new antibiotic of cephamycin group, cefminox (CMNX, MT-141) was studied both fundamentally and clinically in the field of pediatrics.
1. The minimum inhibitory concentrations (MIC) of CMNX for clinical isolates including 24 strains of S. aureus, 15 strains of S. pyogenes, 21 strains of H. influenzae, 24 strains of E. coli, 22 strains of K. pneumoniae and 22 strains of P. mirabilis were determined and compared to those of cefmetazole (CMZ), latamoxef (LMOX), cefotaxime (CTX), cefoperazone (CPZ) and cefazolin (CEZ).
The MIC80 (80% MIC) values of CMNX for H. influenzae, E. coli, K. pneumoniae and P. mirabilis were 1.56, 1.56, 0.39 and 1.56μg/ml, respectively. When compared to antibacterial activities of the control drugs, the activity of CMNX was inferior to those of CTX and LMOX but superior to those of CMZ and CEZ. On the other hand, MIC50, values of CMNX for S. pyogenes and S. aureus were 6.25 and 12.5μg/ml, the activities being inferior to all of CMZ, CTX, LMOX, CPZ and CEZ used as the control drugs.
2. In 3 pediatric patients of 9 to 12 years old, 20mg/kg of CMNX was given intravenously as one shot and serum and urinary concentrations were determined.
The mean serum concentrations in these 3 cases were 124μg/ml, 102μg/ml, 74.0μg/ml, 47.9μg/ml, 20.4μg/ml, 9.2μg/ml and 4.3μg/ml at 1/4, 1/2, 1, 2, 4, 6 and 8 hours, respectively, with a half-life of 1.83 hours. The mean urinary concentrations were 1,968μg/ml at 0-2 hours, 1,205μg/ml at 2-4 hours, 761μg/ml at 4-6 hours and 409μg/ml at 6-8 hours, with 65.4% of the drug dosed recovered from the urine within the first 8 hours on an average.
3. CMNX was used in the treatment of 22 clinical cases including 3 cases of acute purulent tonsillitis, 3 cases of acute bronchitis, 9 cases of acute pneumonia, 5 cases of acute pyelonephritis and 2 cases of acute enteritis. Clinical results in 20 cases excluded of 2 cases of Mycoplasma pneumonia were rated as excellent in 19 cases and as good in 1 case, with an efficacy rate being 100% taking excellent and good cases as effective cases. Bacteriological results for 5 strains of H. influenzae, 1 strain of H. parainfluenzae, 5 strains of E. coli, 2 strains of K. oxytoca and 1 strain of S. pneumoniae revealed that disapperance was obtained for all strains but 1 strain of P. aeruginosa which persisted. The overall eradication rate was 93.3%. In none of the cases symptoms indicative of appearance of side effects were observed. As abnormal laboratory findings elevations in GOT and GPT were seen in 3 cases, that in GOT in 1 case and eosinophilia in 2 cases. However, all of these abnormalities were mild in nature and confirmed to be restored to normal in cases where repeated tests could be performed.
From these fundamental and clinical studies in CMNX in the pediatric field, CMNX was confirmed to be a useful antibiotic of high safety even in children.

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Cefminox (CMNX, MT-141) is a new injectable cephamycin antibiotic, which was studied for its antibacterial activity, absorption and excretion after administration and clinical efficacy of patients with infections. The following results were obtained.
1. Antibacterial activity
The antibacterial activity of CMNX against 19 clinical isolates consisting of 11 species made the results that its activity against E. coli, P. vulgaris and C. jejuni was superior to CMZ and CEZ.
2. Concentration in serum and urine
CMNX was given intravenously to 3 groups at 20mg/kg by one shot (2 cases), 40mg/kg by one shot (2 cases) and 40mg/kg by 1 hour drip infusion (1 case). The half-lives were between 1.15 to 1.80 hours. We obtained over 70% of its excretion to urine within 6 hours after injection.
3. Clinical efficacy
Clinical evaluation was made on a total of 18 patients with various infections, 11 of whom had underlying diseases. The result was excellent in 1 case, good in 11 cases, fair in 2 cases and poor in 4 cases, and the effective rate was 66.7%.
4. Side effect
Clinical and laboratory abnormal findings related to CMNX were not found.
It is concluded that CMNX seems to be effective and safetive antibiotic in the field of pediatrics.

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The authors have carried out the pharmacokinetic and clinical studies of cefminox (CMNX, MT-141). The results were as follows:
CMNX was given by intravenous drip infusion for 1 hour at a dose of 20mg/kg b. w. to 2 children. The serum levels of CMNX were 103.02μg/ml and 77.73μg/ml at 1 hour after drip infusion, and the levels at 7 hours were 4.39μg/ml and 4.19μg/ml, respectively.
The half life times were 1.20 hours and 1.32 hours, respectively.
CSF concentrations of CMNX at 1 hour after drip infusion of a dose of 50 mg/kg in 3 patients with aseptic meningitis were 1.68μg/ml (d. i. for 30 minutes),≤0.25μg/ml (d. i. for 1 hour) and 0.51μg/ml (d. i. for 1 hour), respectively. CSF/serum ratios were 1.1% and 0.6%.
Clinical efficacy was evaluated in 10 cases with purulent tonsillitis (3 cases), pneumonia (3 cases), pyelonephritis (1 case) and enteritis (3 cases). Excellent and good responses were obtained in all cases. Bacteriological response in the form of eradication was noted 8 of 9 cases. No side effects were observed.

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A new antibiotic of cephamycin group, cefminox (CMNX, MT-141), was evaluated clinically in the treatment of bacterial infections in children. The following results were obtained.
1. One case of lacunar tonsillitis (due to H. influenzae) and 5 cases of urinary tract infections (due to E. coli in 2 cases, mixed infection due to E. coli and E. faecalis in 1 case, due to K. pneumoniae in 1 case and causative organism was unknown in 1 case) were treated intravenously with CMNX at daily doses ranging from 58.1 to 122.7mg/kg in 3 divided doses. One case in which the treatment was discontinued after 1 day because of rashes was excluded from assessment of efficacy. Among the remaining 5 cases, CMNX was found ineffective for 1 case of mixed infection due to E. coli and E. faecalis. However, in all of the other 4 cases excellent results were obtained.
2. As side effects, rashes developed in 1 case and slight elevation in GOT in 1 case out of 6 cases.
3. Blood levels following bolus intravenous injection of 20mg/kg of CMNX were 68, 45, 27, 10.2 and 3.1μg/ml at 1/2, 1, 2, 4 and 6 hours, respectively, with T 1/2 of 1.27 hours. The urinary recovery rate within the first 6 hours was 78.6%.

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Cefminox (CMNX, MT-141) was tried in children with various infection and the following results were obtained.
1. Serum levels and urinary recovery of CMNX were studied in 2 patients aged with 9 and 11 years. After intravenous injection of 20mg/kg, the mean serum concentrations at 15, 30 minutes, 1, 2, 4, and 6 hours after the administration were 178.7, 122.2, 73.9, 41.0, 14.0 and 5.3μg/ml, respectively. The half-life in serum was 1.36 hours.
The average urinary recovery rate of CMNX was 86.5% at 6 hours after the administration.
2. The therapeutic efficacy was excellent in 18, good in 1 and poor in 1 patient, the efficacy rate being 95%.
3. As for the side effects, slight elevation of S-GOT and drug fever were observed in 2 cases.

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1. The in vitro antibacterial activity of cefminox (CMNX, MT-141) was nearly equal to that of CTX, LMOX, CMZ and CPZ against the 4 species of clinically isolated strains.
2. CMNX was applied to a total of 17 patients including 11 cases of bronchitis, 4 cases of pneumonia and 2 cases of urinary tract infection. The results showed an efficacy rate of 94% (16/17). In the 4 patients from whom the isolation of pathogenic organisms was possible, the bacteriological response to CMNX was appreciable the efficacy rate being 80% (4/5).
3. No side effect of the drug was observed.

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Cefminox (CMNX, MT-141) was given intravenously to 20 children with the following acute bacterial infections; 10 cases of bronchopneumonia, 4 cases of urinary tract infection, 2 cases of staphylococcal scalded skin syndrome, each 1 case of acute pharyngitis, acute tonsillitis, purulent cervical lymphadenitis and acute tonsillitis, and pleuritis. Good clinical responses were obtained in 18 patients out of 20 patients and bacteriological effectiveness in 13 strains out of 14 strains. No side effect was observed except for 1 case with diarrhea and 1 case with slight elevation of GOT and GPT.
From the above clinical results, it is apparent that CMNX is a useful antibiotic for treating pediatric patients with various kinds of bacterial infections.

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Laboratory and clinical studies were performed as follows on cefminox (CMNX, MT-141), a new cephamycin antibiotic.
1. Pharmacokinetics
Serum concentrations of CMNX were measured in 4 patients given CMNX for prophylactic purpose during cardiac catheterization. In 2 patients given 20mg/kg of CMNX by intravenous bolus injection, the average of peak serum concentration was 178.9 μg/ml at 15 minutes. The mean urinary recoveries in these 2 cases was 66.9% within 6 hours after injection.
In 2 patients given 20mg/kg of this drug by 1 hour drip infusion, the peak serum concentration was obtained at the time drip was completed, and the average value was 68.3μg/ml.
2. Clinical efficacy
CMNX was administrated intravenously to 13 patients in dose of 52.9-96.0mg/kg t. i. d. or q. i. d. for 4-7 days; 3 with tonsillitis, 6 with bronchitis, 1 with bronchopneumonia, 1 with UTI, 1 with lymphadenitis and 1 with enterocolitis. The overall efficacy rate was 92.3%, i. e., efficacy was excellent in 12, and poor in 1.
Bacteriological efficacy was excellent, i. e., 3 of 3 strains disappeared.
Side effects were observed in 3 cases, i. e., 1 case of eruption, 1 case of diarrhea and 1 case of transient eosinophilia.
The above results suggest that CMNX is a useful antibiotic for treating pediatric bacterial infections.

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The therapeutic effects of cefminox (CMNX, MT-141), a new synthetic cephalosporin antibiotic, were examined in the treatment of various pediatric infections. Patients treated were infants and children ranging from 12 days after birth to 12 years old suffering from bronchopneumonia in 10 cases, urinary tract infection in 6 cases, pharyngitis in 2 cases, cervical lymphadenitis in 2 cases, suppurative meningitis, cervical abscess, mastoiditis, peritonitis, bronchitis in 1 case each, total of 25 cases.
As regards method of administration, CMNX from a vial was dissolved in physiological saline or distilled water for injection, and the solution was administered by 3 to 5 minutes one shot intravenous injection (15 cases), or CMNX was diluted with large volume parenteral product and administered by 30 to 60 minutes drip infusion (10 cases).
The dosage of the drug was 21.3 to 165.5mg/kg/day. The administration was continued for 3 to 13 days except 1 case.
As regards clinical efficacy, good or excellent results were obtained in all cases except 3 cases, 1 case was urinary tract infection with cerebral palsy and vesicoureteral reflux, and 1 case was bronchopneumonia with DOWN syndrome and endocardial cushion defect, the other was suppurative meningitis. Total effective rate was 88%. No clinical side effects nor abnormal laboratory findings obviously attributable to CMNX were observed.

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Clinical studies on cefminox (CMNX, MT-141) were conducted and the following results were obtained.
1. Twelve cases of bacterial infections were treated with CMNX with a satisfactory result of “excellent” in 9 and “good” in 3.
2. Antibacterial activity was examined in 7 cases. Pathogenic organisms which were S. aureus,β-Streptococcus, H. influenzae, S. pneumoniae and P. morganii were eradicated in all the cases.
3. Mean maximum serum concentrations of CMNX after intravenous injection of 10, 20 and 40mg/kg were 54.5mcg/ml, 102.3mcg/ml and 202.4mcg/ml, respectively which were obtained 15 minutes after each injection. Mean half-lives of each dose group were 1.60, 1.13 and 1.51 hours, respectively.
4. Mean urinary excretion rates of CMNX at 6 hours after intravenous injection in 10, 20, 30 and 40mg/kg groups were 73.5%, 80.9%, 92.6% and 66.5%, respectively.
5. Side effects were not observed clinically, but anemia in 1 case and eosinophilia in 2 cases were noted in laboratory examination.

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Cefminox (CMNX, MT-141), a newly developed injectable cephem antibiotic, was administered intravenously as one shot injection at 3 different dosages of 10, 20 and 40mg/kg to 9 children; for each dose level 3 children were used. In these children serum and urinary concentrations as well as recovery rates were determined. In addition, in order to determine clinical and bacteriological efficacies of CMNX, it was used in the treatment of 37 cases of various infections consisting of 2 cases of acute tonsillitis, 1 case of acute tonsillitis associated with otitis media, 1 case of acute bronchitis, 1 case of chronic bronchitis, 20 cases of pneumonia, 1 case of pneumonia associated with otitis media, 8 cases of urinary tract infections, 2 cases of purulent lymphadenitis and 1 case of gluteal abscess. The drug was administered intravenously as one shot injection at a mean daily dosage of 76.6mg/kg, in 4 divided doses in most cases, for a mean period of 6 days. Finally, in 43 cases added of 6 drop out cases which were included in analysis of efficacy side effects and abnormal laboratory findings were examined. The following results were obtained.
1. In 9 cases, which received CMNX at 3 different dosages of 10, 20 and 40mg/kg for 3 cases each intravenously as one shot injection, mean serum concentrations reached the peaks of 109.4, 218.1 and 357.1mcg/ml at 5 minutes after injection, respectively, showing dose response relation. The mean half-lives were 1.74, 1.62 and 1.84 hours, respectively.
2. The mean concentrations of CMNX in urine in the same cases as used for determinations of serum concentrations were highest during the 0-2 hours period, reaching 1,582, 3,304 and 4,618mcg/ml at the respective doses. The mean recoveries within the first 6 hours were 82.8, 69.8 and 81.3%, the rate for 20mg/kg group being lower than those obtained for the other groups. This is possibly due to 1 case which showed unusually low recovery rate of 44.4%. When this case is excluded, the recovery rates became similar for all groups.
3. As to clinical results, responses rated as good or higher were obtained for 91.9% of the cases (34 cases/37 cases), with high efficacy rate.
4. No side effects were seen in 43 cases included of drop out cases. Laboratory findings revealed eosinophilia in 6 cases and abnormal elevation of GPT alone in 1 case, of GOT and GPT simultaneously in 1 case and of creatinine in 1 case.

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In a total of 13 children with infections, ranging in age from 1 month to 6 years, cefminox (CMNX, MT-141), a new antibiotic of cephem group, was administered 14 times and its absorption, excretion, clinical results and safety were determined.
Following intravenous drip infusion of CMNX, high blood level was achieved, with half-life of about 1 hour (0.77 to 1.13 hours). The urinary recovery rate was approximately 80% within the first 6 hours after completion of administration.
Clinical results were rated as effective in 8 out of 12 assessable cases (66.7%). In any of the cases treated no side effects developed nor any abnormal changes in laboratory finding were observed. From these results, CMNX is considered to be a new antibiotic useful and safe for use in the field of pediatrics.

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This study was conducted to develop a prolonged action preparation of cefaclor (CCL) which can offer, with the twice-a-day administration, as much effectiveness as its conventional preparation (Kefral® capsule) with the 3 times-a-day administration.
Absorption site of CCL in gastrointestinal tract, preparation form (enteric coated granules) which slowly release CCL, dissolution property of the form, and mixed ratio of the form and rapid release form (nonenteric coated granules) were studied and complex granules consisting of 40% of nonenteric coated granules and 60% of enteric coated granules which dissolve at pH 6 were chosen as a prolonged action preparation of CCL.
Bactericidal activity of the prolonged action preparation (S6472) was confirmed to be the same as that of the conventional preparation by comparative viable cell count study in which concentrations of CCL simulated to plasma concentrations following the administration of S6472 at the dosage of 375 mg b. i. d. and the conventional preparation at the dosage of 250mg t. i. d. were used.
From the above, S6472 is considered to be a prolonged action preparation of CCL which serve our purpose.
Since S6472 can be given with the twice-a-day administration, its daytime administration is not necessary. Therefore, S6472 is considered to be much useful preparation for the patients.

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Current (regular) preparation of cefaclor (CCL) require the 3-time-a-day administration. S6472 (sustained release preparation) which can be used with the twice-a-day administration in the morning and the evening is capsule and granule preparations consisting of 40% of nonenteric and 60% of enteric coated granules of CCL.
Phase I clinical studies of S6472 were conducted in 12 nonfasted healthy adult male volunteers with cross over method using a single dose of 375mg in capsule and granule forms of S6472, and 250mg in capsule form of regular CCL as a control drug. The volunteers received the 3 preparations at 1-week interval. The summary of the results from the above studies is as follows:
1. Grouping of the volunteers
The 12 volunteers were divided into 3 groups (each group consists of 4 volunteers) and there were no significant differences between each group regarding background factors of the volunteers.
2. Tolerance
None of the volunteers who received the 3 preparations at 1-week interval complained of subjective abnormalities. No abnormalities which are considered to be due to S6472 and regular CCL were found in the clinical laboratory tests carried out before the administration and 1 week after the completion of the studies.
3. Plasma level
There were no significant differences between capsule and granule forms of S6472 regarding C_max and AUC, and it was confirmed that bioavailability of both preparations was the same. It was also confirmed that plasma levels of the 2 preparations of S6472 were maintained for longer period of time than those of regular CCL.
4. Urinary excretion
Mean urine levels of the 2 preparations of S6472 every 2 hours after the administration were confirmed to be maintained for longer period of time than those of regular CCL. There were no significant differences between the 2 preparations of S6472 regarding urinary recovery rate. However, the significant differences between the 2 preparations of S6472 and regular CCL were observed. Urinary recovery rate of the 2 preparations of S6472 was 87-88% of that of regular CCL.

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In order to see absorption and excretion of S6472 (sustained release preparations of cefaclor (CCL)), 3 studies regarding, 1) influence of meals (single dose of 375mg in capsule form), 2) dose response (single dose of 375mg vs. 750mg in granule form) and 3) continuous administration (twice-a-day administration of 750mg in granule form for 8 days) were conducted in 15 healthy adult male volunteers using capsule and granule forms of S6472. The following is the summary of the results from the above studies:
1. Tolerance
In the above 3 studies, none of the 15 volunteers complained of subjective abnormalities. In the clinical laboratory tests performed before the administration of S6472 and at the next day of the completion of the studies, the values from the laboratory tests were within normal range.
2. Influence of meals
The average time for peak plasma level of CCL and decrease in the plasma level following the administration of S6472 were the fastest in the fasted volunteers, followed by the volunteers with light meals and usual meals. From this, it was confirmed that plasma levels of CCL were maintained for longer period of time in the non-fasted volunteers than in the fasted volunteers. In the volunteers who had light and usual meals, the peak plasma levels, AUC of the plasma levels and urinary recovery rate were almost the same. Influence by amount of meals was scarcely observed.
3. Dose response
Mean serum levels and their AUC in the volunteers receiving 750mg of S6472 were approximately twice as much as those in the volunteers receiving 375mg of S6472, and dose response between the 2 doses was confirmed.
4. Continuous administration
Mean serum levels and their AUC at the first dose and the 15th dose (final dose) were almost the same. In the continuous administration of S6472 for 8 days (15 doses), no accumulation of CCL in the body was observed.

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1. A study in which 375mg of S6472 was orally given to 3 healthy adult volunteers before a meal, after a light meal, and after a usual meal in the cross-over method revealed the highest levels, both in serum and urine, in cases treated before a meal. In cases administered after a light or square meal, the serum level was less, but approximately 2μg/ml over 6 hours after administration. No difference was seen in the AUC.
2. The effective rate of S6472 when given at 750-1,500mg/day was 74.6% in 62 patients with skin or soft tissue infectious diseases.
3. Neither subjective or objective adverse reactions were seen in any case. Clinical laboratory testing revealed 1 case each of anemia and increased BUN, for which S6472 was not responsible.

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Fundamental and clinical studies of S6472 (sustained release preparation of cefaclor (CCL)) were conduct-ed in the surgical field and it was confirmed that the preparation is a useful drug. The following is the summary of the results from the fundamental and clinical studies:
1. In vitro antibacterial activity CCL showed MICs of 0.78 to 6.25 μg/ml against almost strains of S. aureus, E. coli and Klebsiella isolated from surgical wound regions, and the antibacterial activities were stronger than those of cephalexin (CEX).
2. Clinical efficacy S6472 was orally administered to 33 patients with skin and soft tissue infections in 2 divided doses. As a result, excellent clinical response was observed in 13 patients, good response observed in 14 patients, fair in 4 and poor in 1. The clinical efficacy in 1 of the 33 patients was unknown. Overall clinical effective rate was 84.4%.
3. Adverse reaction In 2 patients, mild gastrointestinal symptoms were observed.

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Fundamental and clinical studies on S6427, a new prolonged acting preparation of cefaclor, were per-formed and the following results were obtained.
1. Serum level and urinary excretion 750 mg of S6472, 500 mg of cefaclor (CCL) and 500 mg of cephalexin (CEX) were orally administered in 6 healthy adult volunteers by the cross over method to measure serum level and urinary excretion.
The serum level-time curve of S6472 showed 2 peaks at 1 and 6 hours after administration. The peak serum level of S6472 was 4.2μg/ml and 2.9μg/ml, respectively, 1 and 6 hours after administration.
The peak serum level of CCL and CEX was 5.8μg/ml and 12.1μg/ml, respectively, 2 hours after administration.
The urine level-time curve of S6472 also showed 2 peaks at 0-2 and 4-6 hours after administration and the peak urine level was 1,320μg/ml and 994μg/ml, respectively, 0-2 and 4-6 hours after administra-tion.
The peak urine level of CCL was 1,337μg/ml, 0-2 hours after administration and that of CEX was 2,079μg/ml, 2-4 hours. The mean urinary excretion of S6472, CCL and CEX was 56%, 69% and 94% of dose at 12 hours after administration.
2. Clinical evaluation
S6472 was tried in 200 cases of various urinary tract infections. For one group of 85 cases with acute uncomplicated cystitis, clinical effects were evaluated as excellent in 40 cases, moderate in 42 cases and poor in 3 cases, and the overall clinical effectiveness rate was 96.5%.
For another group of 68 cases with complicated urinary tract infection, clinical effects were evaluated as excellent in 9 cases, moderate in 27 cases and poor in 32 cases, and the overall clinical effectiveness rate was 52.9%.
3. Side effects
Side effects were observed in 7 cases with diarrhea, epigastralgia, stomatitis, eruption and facial swelling. Administration of S6472 was discontinued in 2 cases, but in 7 cases all symptoms were transient.

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