Fundamental and clinical studies on cefpimizole (AC-1370), a new cephalosporin derivative, in the field of obstetrics and gynecology have been investigated, and the following results were obtained.
1. High concentrations of AC-1370 in internal genital organs were detected after intravenous administra-tion of 1.0g of AC-1370.
2. In the treatment of 14 cases of infection, the therapeutic effects were excellent or good in 11 cases and overall efficiency rate excluding 1 case with side effects was 84.6% (11/13).
3. No serious side effect was observed except 1 case of nausea and vomiting.

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Clinical study to evaluate the usefulness of cefpimizole (AC-1370) was made in the 6 patients with female genital organ infections. Two grams or 4g of AC-1370 was administered a day by intravenous drip infusion ranging from 5 to 18 days. Responses were excellent in 2 cases, good in 3 cases and poor in 1 case, parametritis after hysterectomy. The efficacy rate was 83%.
Neither general side effect nor abnormal laboratory finding was observed.
AC-1370 showed a satisfactory clinical efficacy in treatment of the infections in the field of gynecology, and it has been concluded that AC-1370 will be an useful antibiotic for these infections.

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Cefpimizole (AC-1370) was administered to 5 cases with uterine myoma before hysterectomy, and tissue distribution was determined. AC-1370 was also administered to 5 cases with gynecological infections. The following results were obtained.
1. One gram of AC-1370 was administered from 43 to 299 minutes before hysterectomy, tissue distribution of AC-1370, such as ovary, oviduct, myometrium, cervix uteri, and portio vaginalis was showed the highest level (30.0-49.5μg/g) at 43 minutes after administration, and these were 39.0-64.4% of the concentration in uterine arterial blood. Tissue concentration of AC-1370 was then gradually decreased following with the decreasing of the concentration in uterine arterial blood.
2. AC-1370 was administered to 3 cases with pyometra, 1 case with BARTHOLIN abscess, 1 case with adnexitis. The clinical efficacy was good in all 5 cases. Bacteriological study revealed that A. faecalis and E. coil were eradicated, but B. fragilis was persisted. No side effect was observed in all cases.

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We made fundamental and clinical studies of a new cephalosporin derivative, cefpimizole (AC-1370).
AC-1370 was relatively efficiently transferred into the uterus and uterine adnexa; in other words, it was as well transferred into the tissues as the other cephalosporin derivatives. There seemed to be no specific relation between its blood level and its level in any tissue.
In 1 patient treated with AC-1370 for postoperative infection, clinical findings, WBC and CRP improved: the drug was evaluated as effective.
Neither hepatic nor renal function was impaired in the patients treated with AC-1370 in the fundamental and clinical studies of the drug.

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Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, and the following results were obtained.
1. The absorption and tissue penetration of AC-1370 into intrapelvic genital organs were good. The peak serum level in the uterine artery after an intravenous drip infusion for 30 minutes was 49.0μg/ml. High concentrations were obtained also in genital organ tissues; the maximum concentrations were 24.4-39.0μg/g after an intravenous drip infusion. The changing patterns of the tissue concentrations were similar to those in the serum.
2. The penetration of AC-1370 into intrapelvic dead space exudate was good. The level reached a peak of 35μg/ml at 2-4 hours after an intravenous drip infusion with 1g and 3.7μg/ml after 12 hours.
3. AC-1370 was effective in 20 out of 21 cases (95.2%) with gynecoobstetrical infections such as intrauterine, intrapelvic infection and mammitis, administered with 1-2g twice a day. Few side effects were observed.

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Cefpimizole (AC-1370) was studied for its transference into adnexa uteri and uterine tissues as well as for its effects and safety on gynecological infections. The results obtained are as follows:
1. Peak levels of AC-1370 were obtained in the antecubital vein and uterine artery at 10 minutes, in the tissues of adnexa uteri and uteri about 30 minutes after one shot intravenous injection of AC-1370 1g, and relatively high concentrations were maintained for several hours.
2. In the treatment of 30 cases of gynecological infections, the clinical efficacy of AC-1370 was assessed as effective in all cases.
3. As for the bacteriological effects of AC-1370, 77.6% of isolated organisms were eradicated and 90% of all cases were effective.
4. Side effects and abnormal laboratory findings due to AC-1370 were not observed during and after administration.

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We made fundamental and clinical studies of a new cephalosporin derivative cefpimizole (AC-1370), and found the following.
In 7 patients treated with AC-1370 for the fundamental study of the drug, the blood level of the drug in the uterine artery scarcely differed from that in the elbow vein, and it decreased steadily with time. It remained to be 6.5-7.0μg/ml 5 hours after intravenous injection of 1g of the drug.
The tissue-serum concentration ratio of the drug was 122-58% in the portio vaginalis where the drug was transferred at the highest level, and 56-114% in the oviduct where it was transferred at the lowest level; the mean level was 61.5%.
The responses to AC-1370 of 10 patients with genital infections were excellent in 1, good in 8 and poor in the other, with a response rate of 90%.
Bacteriologically, pathogens were eradicated in 3, decreased in 2, and the response was unknown in the other 5.
No side effects or abnormal laboratory findings were noted except for leukopenia in 1 patient.

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Cefpimizole (AC-1370), a new cephalosporin antibiotic, was evaluated for its distribution in uterine tissue, penetration into retroperitoneal exudate and therapeutical effects on some infections in gynecology. The following results were obtained;
1. The levels of AC-1370 in the cubital vein were similar to those in the uterine artery and this remained in the course of examinations after an 1 g intravenous injection.
2. Seven patients with gynecological infections received AC-1370 by intravenous injection. The overall efficacy rate was 85.7%.
3. No adverse reaction was observed in any of the cases treated with AC-1370, nor was there any marked changes in the laboratory findings.

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Cefpimizole (AC-1370) concentrations in the pelvic dead space exudate were determined in patients under-going curative resection of carcinoma of the uterine cervix to study the transfer of the drug into the female genital organs, and the results were statistically analyzed, using the two-compartment model. When 1g of AC-1370 was administered by intravenous drip infusion over 1 hour, the AC-1370 concentration in the serum from the antecubital vein reached a level of 129.09μg/ml at 1 hour of intravenous drip infusion, and the AC-1370 concentration in the pelvic dead space exudate reached a peak of 30.32μg/ml at 2.51 hours of intravenous drip infusion, and remained at not less than 12μg/ml 8 hours after the beginning of the drip infusion, with the area under the curve (AUC) for the AC-1370 concentration in the pelvic dead space exudate being 213.66μg·hr/ml.
Seven patients with obstetrical and gynecological infections were treated with 1g of AC-1370 by intravenous drip infusion over 1 hour, 2-3 times daily. Although the patients all had rather mild infections, the treatment was effective in all of them.
The findings in this study proved a dose of 1g of AC-1370 at a time to be sufficiently effective in mild cases, but in view of the transfer of the drug into tissues, it seemed necessary to administer 2g of the drug at a time in severe cases.

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Cefpimizole (AC-1370), a new cephem antibiotic, was studied clinically in the field of obstetrics and gyne-cology, and the following results were obtained.
1. AC-1370 was administered to 7 patients with gyneco-obstetrical infections, and the therapeutic efficacy was 85.7% (6 cases of 7 cases).
2. E. coli was isolated as causative pathogen in 4 cases out of 7 cases, and was eliminated in all cases after the AC-1370 treatment. S. faecalis was eliminated in 2 cases out of 3 cases, and B. fragilis was eliminated in all 3 cases.
3. As abnormal laboratory findings, transient elevation of GOT, GPT and Al-P was observed in 1 case but became normal after cessation of AC-1370 administration. The therapeutic effect was poor for this case.

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Fundamental and clinical studies on cefpimizole (AC-1370), a new cephem antibiotic, were performed and the following results were obtained:
1. Concentration of AC-1370 was examined in serum, internal genital organs and retroperitoneal fluid after single intravenous administration of 2.0g dose.
The venous serum level of AC-1370 was 243μg/ml at 30 minutes after the administration.
The sufficient transfer of AC-1370 to internal genital organs and retroperitoneal fluid was recognized.
2. In clinical trial, AC-1370 was given to 10 cases with obstetrical and gynecological infections.
The efficacy was evaluated as good in 8 cases and poor in 2 cases.
No side effects were observed in any of the cases treated with AC-1370.

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The findings from fundamental and clinical studies on cefpimizole (AC-1370) in the treatment of infections in obstetrics and gynecology are reported.
We investigated the transfer of AC-1370 into female genital tissues of 6 patients and the transfer of the drug into the pelvic dead space exudate in 9 patients by means of determining its concentrations in the tissues 90 to 210 minutes after the end of intravenous drip infusion of the drug over 1 hour. The mean concentration was 13.06μg/g for the oviduct, 16.50μg/g for the ovary, 16.50μg/g for the endometrium, 14.92μg/g for the myometrium, 16.58μg/g for the uterine cervix, 17.75μg/g for the portio vaginalis, 10.46μg/ml for the uterine arterial serum and 9.91μg/ml for the antecubital venous serum.
The drug proved to be well transferred into the pelvic dead space exudate; it reached a peak of mean 2 hours after the end of the intravenous drip infusion of the drug over 1 hour, then decreased steadily, and was found to be a mean of 16.7μg/ml even 8 hours after the end of the intravenous drip infusion.
Four patients with infections in obstetrics and gynecology were then treated with AC-1370. Three out of the 4 patients responded to the treatment, while the response of another patient was unknown. None of the 4 patients showed any side effects of the drug or any abnormalities in laboratory findings.

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The findings from recent fundamental and clinical studies of the efficacy of cefpimizole (AC-1370) in obstetrics and gynecology are reported in this paper.
The AC-1370 concentrations in genital tissues sampled 30 to 56 minutes (a mean of 41.4 minutes) after intravenous injection of 1g of the drug were 14 to 76μg/g (a mean of 32.4μg/g). The mean transfer ratios of the drug into the genital tissues to the concentration in the uterine arterial blood were such that the transfer ratio into the portio vaginalis was the highest, followed by the uterine cervix and the myometrium, and that into the oviduct was the lowest with about 1/2 that into the portio vaginalis. The concentration in the antecubital venous blood and that in the uterine arterial blood remained similar for all patients. The transfer of AC-1370 into the pelvic dead space exudate reached a peak (49.5μg/ml) 1 hour, and also a peak (49.8μg/ml) 2 hours after the intravenous injection. It then decreased gradually, but remained high, being higher than that in the antecubital venous blood about 50 minutes after the intravenous injection.
Ten patients with infections in gynecology were treated with 1.0 to 4.0g daily of AC-1370, to a total dose of 6 to 52g, over a period of 3 to 13 days. One of them showed excellent response, 8 showed moderate response, and another showed poor response to the treatment: in other words, a response rate of 90% was achieved. Bacteriologically, pathogens were eradicated from 3 and decreased in 3, and microbial substitution occurred in another patient.
No side effects of the drug were observed except for eruption in 1 patient. None of the 10 patients showed any abnormalities in laboratory findings.
From the present fundamental and clinical studies of AC-1370, we have drawn the conclusion that the drug is one of extremely useful antibiotics in the treatment of infections in obstetrics and gynecology.

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Cefpimizole (AC-1370), a new cephem antibiotic, was studied in the field of obstetrics and gynecology, fundamentally and clinically. And the following results were obtained.
1. The concentrations of the drug in uterine arterial and cubital venous blood, and internal genital organs following intravenous drip infusion were measured. The results demonstrated favourable transfer of the drug into the various internal genital organs.
2. Four patients with obstetric and gynecological infections were treated with AC-1370. The therapeutic results were good in 3, and poor in 1 case, therefore the effective rate was 75%. No side effects were noted in any cases, but the severe eosinophilia (37%) was found in 1 patient. It is therefore presumed that AC-1370 is a useful drug for infectious diseases in the field of obstetrics and gynecology.

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The use of cefpimizole (AC-1370) in 11 patients with a variety of obstetric and gynecologic infections was studied. Although the activity of AC-1370 was found in vitro less eminent than those of currently employed antibiotic regimens, the overall clinical response was 82%. No side effects were found.

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In vitro synergistic activities of astromicin (ASTM), a new aminoglycoside antibiotic, combined with β-lactam antibiotics (cefsulodin (CFS), cefoperazone (CPZ), latamoxef (LMOX)) were investigated against P. aeruginosa by the checkerboard technique, FIC index and the killing curve.
FIC indexes of ASTM in combination with β-lactam antibiotics against 11 fresh clinical isolates of P. aeruginosa, P. aeruginosa BMH No.1 and E-2 were synergistic or partially synergistic in most cases.
Checkerboard of P. aeruginosa BMH No.1 and E-2 to ASTM and 3 β-lactam antibiotics showed the synergism, too.
Bacteriostatic concentrations of ASTM, CFS, CPZ or LMOX showed synergistically bactericidal effects when these antibiotics were added in combination to the culture of P. aeruginosa BMH No.1.

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Ceftizoxime (CZX) was used for 33 patients with respiratory tract infections; 22 patients with pneumonia, 3 patients with pulmonary abscess, 4 patients with diffuse panbronchiolitis and 4 patients with acute exacerbation of bronchiectasia.
Clinical effects of CZX were evaluated in 33 patients; excellent in 16 and good in 14 patients. The efficacy rate was 91%. Bacteriological effects of CZX were prominent in 7 patients infected with S. pneumoniae, H. influenzae, K. pneumoniae and Citrobacter, but not in a patient infected with P. aeruginosa. The elimination rate was 92% (12/13).
As the side effects, exanthema in 1 patient and gastrointestinal symptoms (nausea and vomiting) in 1 patient were observed. However, they improved without any treatment by cessation of CZX use. Abnormal laboratory findings were observed in 2 patients with elevated GOT and/or GPT. They normalized after cessation of drug.
The usefulness of CZX was 82% (27/33). Therefore, CZX is a very useful drug and its effects are promising in clinical management of respiratory tract infections.

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Fundamental, clinical studies on cefoperazone (CPZ), a new synthetic antibiotic of cephalosporins was conducted to obtain results as follows.
1. This preparation, 11.4-50mg/kg was administered to 11 cases of children by intravenous drip infusion for 30minutes, and serum levels were studied. The highest serum level at the completion of infusion was 40.0-138.0mcg/ml. A dose response was observed. The half-life in serum averaged 1.55 hours except 2.4 hours observed with 1 case of liver dysfunction.
2. When the urinary excretion during 30 minutes drip infusion was examined, the urinary recovery rate at 0-6 hours in 2 cases of children averaged 17.2% and was low at 5.3% in 1 case of membranoproliferative glomerulonephritis.
3. In terms of the clinical effect on bacterial infections in pediatric field, CPZ proved effective in all of the 21 cases in which it was used alone. And it showed an excellent antibacterial activity against all the bacteria isolated from cases used as the subjects.
4. When side effects were studied, diarrhea and slight impairment of the liver were observed, but all were transient.
5. As a result of a study on the renal toxicity of CPZ, CPZ was deemed as being a drug which hardly causes disturbance of renal tubules judging from the aspect of the β-D-N-acetylglucosaminidase activity in urine and variations in the urine β₂2-microglobulin levels.

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A newly developed product, KS-R1 (a suppository containing 250mg potency of ampicillin (ABPC)), was given to 7 children (5 boys and 2 girls) ranging from 4 years and 5 months to 8 years and 10 months in age, 3 times a day (average daily dose, 62.4mg/kg) for 5 days.
As a control, the same amount of ABPC dry syrup was given orally to 7 children (4 boys and 3 girls) ranging from 2 years and 8 months to 7 years and 7 months in age, 3 times a day (average daily dose, 55.3mg/kg) for 5 days.
The effects of these 2 preparations on the bacterial flora of the feces were investigated, and concentrations of ABPC in the feces and sensitivities of the isolated strains to ABPC were determined. The results were as follows.
1. As for Gram-negative bacilli in the feces from children given KS-R1, there was no change in Escherichia coli, Klebsiella sp., Citrobacter sp. and Enterobacter sp. which were isolated from many children 3 days after the end of treatment, but they did not show any constant pattern of change in mean number. Other species did not show any pattern of increase in the number of children from whom they were isolated, or in the number of bacteria during the course after the beginning of treatment. The total number of bacteria identified as Enterobacteriaceae was at the level of 10⁸ cells/g on any day of examination. Of Gram-negative bacilli other than Enterobacteriaceae, Pseudomonas sp. showed no constant pattern of change in number. On the other hand, of Gram-positive bacteria, there was no constant pattern of change in the number of Staphylococcus aureus, Coagulase-negative Staphylococci began to be isolated from many children 5 days after the beginning of treatment and were isolated from all children 5 days after the end of treatment, but there was no tendency for the mean number to increase. Enterococcus sp. was not isolated from 3 children 3 days after the beginning of treatment, and was decreased in number by one order in 3 out of other 4 children as compared with before-treatment. However, this species was isolated from all children 3 days after the end of treatment, and the mean number of bacteria was similar to that before-treatment although the number of bacteria was different in individual children. There was no constant pattern of change in the number of cells of Candida sp. In anaerobes, Bacteroides sp. was at the level of 10⁹ cells/g, and the total number of anaerobes was also at the level of 10⁹-10¹⁰ cells/g, showing no effect of KS-R1.
2. As for Gram-negative bacilli in the feces from children given ABPC orally, there was no effect on E. coli, just as with KS-R1.
Klebsiella sp., as in the case of administration of KS-R1, was isolated from many children 3 days after the end of treatment, but the mean number was not greater than that on any other day of examination. Citrobacter sp., Enterobacter sp. and other species also showed no constant pattern of change in the number of bacteria. The total number of Enterobacteriaceae was at the level of 10⁸-10⁹cells/g, the same as with administration of KS-R1. As for Gram-negative bacilli other than Enterobacteriaceae, Pseudomonas sp. was isolated from 1 or 2 children on several days of examination, but there was no constant pattern of change in the number of bacteria. On the other hand, for Gram-positive bacteria, the results with S. aureus and Coagulase-negative Staphylococci were similar to those in the case of administration of KS-R1. The latter was isolated from more children day by day, but there was no constance of change in the number of bacteria. In most children, Enterococcus sp. was not isolated or was decreased 3 days after the beginning of treatment, but variation in the mean number was within 10⁷-10⁹ cells/g.

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Following the previous report on pharmacokinetics of micronomicin (MCR) in healthy volunteers, pharmacokinetic studies were made again in patients with different degree of renal impairment, and a nomogram was obtained.
1. Methods MCR at a dose of 60mg/time was given by 1-hour drip infusion to 14 inpatients who consented to receive MCR (age: 35 to 84 years, Ccr: 17.96 to 104.35ml/min). The blood collection was performed in accordance with the schedule made upon the degree of renal impairment, and the serum concentration was determined by HPLC method. The results were analyzed by MULT program using two-or one-compartment open model.
2. Results
The serum concentration (C_max) just after administration of MCR was 5.8±0.9μg/ml (mean±S. D.). The biological half-life was 1.81 to 12.35 hours. Taking the above results into consideration together with the previous ones of healthy males, the following correlation was obtained between the elimination constant (Kel or β) and Ccr calculated from S-Cr.:
Kel or β=0.0038×Ccr-0.0097
Further, no side effect was observed in these studies.
3. Conclusion Elimination of MCR from blood was dependent on renal function like other aminoglycosides, and so it was possible to estimate the elimination constant from Ccr. From these results, a nomogram for the optimum dosage regimen of MCR was obtained.

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The pharmacokinetics of bacmecillinam (KW-1100), a new semisynthetic penicillin, was studied. Plasma levels, tissue distribution, metabolites and urinary and biliary excretion of mecillinam after oral administration of KW-1100 were studied in rats given a dose of 20mg/kg (as mecillinam).
1. The absorption of ¹⁴C-KW-1100 was so rapid that the level in blood was found to reach the peak 30 minutes after administration.
2. ¹⁴C-KW-1100 was distributed widely into various tissues and relatively high distribution was noted in liver, kidney, adrenal gland and spleen.
3. No accumulation of ¹⁴C-KW-1100 in any tissue was found. It was excreted rapidly from each tissue.
4. Within 24 hours after administration of KW-1100, approximately 86% of the given dose was excreted. And within 72 hours, approximately 97% of the dose was excreted. Excretions in urine and feces within 72 hours after KW-1100 administration were 39.5 and 57.4% of the given dose, respectively. Biliary excretion was 2.0% of the given dose within 24 hours after administration of KW-1100.
5. The major metabolite in the plasma at peak time (30 minutes) was mecillinam (50.5%). The major metabolite in the urine (0-8 hours) was mecillinam (52.2%), too. The minor metabolites were 5, 5-dimethyl-2-(1'-formamidomethyl)-thiazolidine-1, 4-dicarboxylate(M-1), 6-β-[(hexahydro-1H-azepin-1-yl)]-methylenearninoi-penicilloic acid (M-6) and M-4.

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The placental transfer and transition into milk of bacmecillinam (KW-1100), a new semisynthetic penicillin, have been studied with ¹⁴C-KW-1100 administered orally in the pregnant and lactating rats, respectively.
The level of ¹⁴C-KW-1100 in the umbilical cord blood was 7.2% of the peak maternal blood level and the radioactivity was eliminated slowly. At the peak fetus level (4 hours after administration), the radioactivity transfered into the fetuses was found to be 0.01% of the dose.
¹⁴C-KW-1100 was distributed into the uterus, ovary, placenta and consistently into the fetal membrane. ¹⁴C-KW-1100 was excreted into milk slightly, and the concentration of radioactivity in milk did not exceed the maternal peak blood level.

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The pharmacokinetics (i. e., blood level, biological half-lives and excretion) of bacmecillinam (KW-1100) was investigated. KW-1100 was orally administered to dogs at the dose of 20mg/kg (as mecillinam).
1. Biological half-lives (radioactivity) of ¹⁴C-KW-1100 in plasma were 1.2 hours (T1/2α) and 52 hours (T1/2β). The C_max and T_max were 8.4μg/ml and 2 hours.
2. The biological half-life (microbiological activity) of KW-1100 in plasma was 0.9 hour. The C_max and T. were 5.6μg/ml and 1 hour.
3. The urinary and fecal excretion of ¹⁴C-KW-1100 were approximately 46% and 49% (0-72 hours), respectively.
4. The major metabolites in the urine (0-8 hours) were mecillinam, 5, 5-dimethy1-2-(1'-formamido-methyl)-thiazolidine-1', 4-dicarboxylate (M-1) and 6-β-[(hexahydro-1 H-azepin-1-yl)-methyleneamino]penicilloic acid (M-6), each distribution ratio of which was 57.2, 24.2 and 12.0% of the total radioactivity in the sample, respectively.
5. The major metabolite in the plasma at peak time (2 hours) was mecillinam (56.2%).

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Bacmecillinam (KW-1100) metabolites and their excretion in human urine were investigated in the 3 male volunteers. After administration of KW-1100 capsules containing 80mg (2×40mg) as mecillinam to men, the urine samples up to 8 hours were collected for every 2 hours and analysed by high performance liquid chromatography and gas chromatography.
The major metabolites in the human urine were mecillinam and 6-β-[(hexahydro-1H-azepin-1-yl)-methyl-eneamino]-penicilloic acid (M-6), and minor quantities of M-4 and M-1 were also detected as the metabolites. Total recoveries of administered dose for the 3 volunteers were approximately 62, 81 and 73%, respectively. And M-1 excretion rate was lower than that in the case of rats and dogs. Hexamethyleneimine (HMI) as metabolite from the side chain was detected.

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In vitro viable cell count studies of sustained release preparations of cefaclor (CCL) conclude that the mixture of nonenteric and enteric coated granules of CCL in the ratio of 4 to 6 is the most appropriate form (4:6 form) for the sustained release preparation of CCL. In order to clinically confirm the above conclusion, comparative double blind clinical studies of 3 mixture forms (2:8, 4:6 and 6:4 forms) with a regular preparation (CCL form) were conducted in dental infections regarding efficacy, safety, and usefulness of the 4 forms. Evaluable cases for efficacy and usefulness were 364 in total (96 cases for the 2:8 form group, 89 cases for the 4:6 form group, 89 cases for the 6:4 form group, and 90 cases for the CCL form group). Evaluable cases for safety were 404 cases in total (102 for the 2:8 form, 100 for the 4:6 form, 102 for the 6:4 form, and 100 for the CCL form). Daily dose of the 3 forms of sustained release preparations was 375mg b. i. d. after breakfast and dinner and that of the CCL form 250 mg t. i. d. after breakfast, lunch and dinner. Following are the results of the clinical studies:
1. There were no significant differences among the 4 patient-groups (2:8 form, 4:6 form, 6:4 form, and CCL form) regarding background factors of the patients and findings of their subjective and objective symptoms before the initiation of the administration, and it was therefore confirmed that there were no problems in conducting the comparative double blind clinical studies.
2. Overall clinical effective rate determined by the efficacy evaluation criteria of the Japanese society of oral surgery (JSOS) were 89.5% at day 3 and 94.8% at day 5 in the 2:8 form group, 87.4% at day 3 and 95.5% at day 5 in the 4:6 form group, 86.4% at day 3 and 91.0% at day 5 in the 6:4 form group, and 93.3% at day 3 and 96.7% at day 5 in the CCL form group. The effective rate determined by the physicians who actually treated the patients were 84.4% in the 2:8 form group, 87.6% in the 4:6 form group, 84.1% in the 6:4 form group, and 87.8% in the CCL form group. In both judgments by the efficacy evaluation criteria of JSOS and the physicians, there were no significant differences among the 4 forms regarding overall clinical efficacy.
3. In judgments at day 3 and day 5 by the efficacy evaluation criteria and judgment by the physicians, there were no significant differences among the 4 forms regarding clinical efficacy by diseases, degree of their severity and other conditions.
4. There were no significant differences among the 4 patient-groups regarding findings of systemic and subjective symptoms by treatment days. However, the objective symptoms “swelling outside mouth” at day 1 in the 6:4 form group, and “induration” at day 3 in the 2:8 form group were worse than those in the CCL form group.
5. Incidence of side effects was 3.9% in the 2:8 form group, 5.0% in the 4:6 form group, 6.9% in the 6:4 form group, and 4.0% in the CCL form group. There were no significant differences among the 4 groups regarding the incidence of side effects. Major side effects observed were mild or moderate gastrointestinal symptoms.
6. The degree of usefulness of the 2:8 form, the 4:6 form, the 6:4 form and the CCL form were 85.4%, 84.3%, 84.1% and 78.9%, respectively. There were no significant differences among the 4 forms regarding the usefulness.
From the above results, although it could not be decided which form was the best one for the sustained release preparation of CCL, efficacy, safety and usefulness of the 3 sustained release preparations with the twice-a-day administration after breakfast and dinner proved to be comparable to those of the regular preparation with the three-time-a-day administration.

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Serum and/or urine levels of cefaclor (CCL) were studied in 4 patients during the therapy with CCL.
In patients with severely impaired renal function, moderately higher serum and urine levels of CCL persisted, serum half-lives of CCL were moderately prolonged and urinary excretion of CCL slightly decreased.
Although dosage modification of CCL is necessary in patients with renal dysfunction, multiple doses of 250mg every 8 hours may be safe and effective even in patients with impaired renal function.

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