In order to evaluate objectively the clinical efficacy and side effects of a new oxacephem antibiotic “6059-S”, a well-controlled study was carried out using Sulbenicillin (SBPC) as a control drug in patients with complicated urinary tract infection. 1g of 6059-S or 5g of SBPC was injected intravenously (drip infusion) twice a day (2 g of 6059-S or 10g of SBPC per day) for consecutive 5 days. Both drugs were administered to 244 patients, and the clinical efficacies of 108 patients who were administered 6059-S and of 102 patients who were administered SBPC were able to be evaluated completely according to “Criteria for Evaluation of Efficacy of Antimicrobial Agents on Urinary Tract Infections”.
The overall effectiveness rate of 6059-S group with single infection was 77.5% (55/71 patients) and that of SBPC group was 52.7%(29/55 patients). This effectiveness rate of 6059-S group was significantly superior than that of SBPC group by statistical analysis. Concerning to mixed infection, the patients were separated into two groups, one group was the patients with indwelling catheter and another group was the patients without indwelling catheter. As to catheter indwelling group, the effectiveness rate of 6059-S group was 58.8% (10/17 patients), which was significantly superior than that of SBPC group (25.7%, 9/35 patients). As to the group without indwelling catheter, the effectiveness rate of 6059-S group was 70.0% (14/20 patients) and that of SBPC group was 83.3% (10/12 patients). There was no significant dierence between those effectiveness rates. Bacteriologically, the eradication rate of 6059-S group against E. coli was 95.5%, and 81.0% against S. marcescens and 78.6% even against Pseudomonas species. Against all species of bacteria except for S. faecalis, 6059-S was confirmed to show the excellent eradication rate.
The subjective side effects were observed in 0.8% (1/124 patients) of 6059-S group and in 2.5%(3/120 patients) of SBPC group, and deterioration in laboratory hematological test values were observed in 2.7% (3/113 patients) of 6059-S group and 3.6% (4/112 patients) of SBPC group. There were no significant dierence between the side effects of both groups of drug. All side effects were transient and not serious.
Based on the above results, 6059-S was considered to be less toxic, safe and clinically extremely useful drug for the treatment of complicated urinary tract infections.

View full abstract

An intramuscular injection of dibekacin (DKB) of more than 240 mg/kg induced remarkable acute renal damage in dehydrated rats deprived drinking water for 24hrs. When such rats previously received an oral administration of glucaron of more than 75 mg/kg, the induction of the dysfunction was aignificantly inhibited as measured the blood urea nitrogen contents. Accumulation of DKB in the blood and kindneys of rats receiving the repeated injections of the chemotherapeutic dose (130 mg/kg) was also inhibited by the combination with 600 mg/kg glucaron. In spite of such effects, antibacterial activity of DKB in vivo and in vitro was not quite influenced by the inhibitor.

View full abstract

Bactericidal activity of cefazolin, cefoxitin and cefmetazole against clincial isolates of E. coil and K. pneurnoniae was investigated:
The mean geometric MICs of cefmetazole against 200 strains each of the test organism were lowest, followed in descending order by those of cefazolin and cefoxitin. The killing activity at the fixed concentrations of 5 and 50μg/ml of cefazolin and cefmetazole was almost the same, but was stronger than that of cefoxitin.
In the kinetic model under the conditions simulating serum levels of the two drugs in humans after i. v. injection (1g), cefazolin was strongest in bactericidal activity of the three drugs. The results indicate that the highest and most prolonged serum concentrations of cefazolin refrected the strong bactericidal activity and the longest inhibition period of the bacterial regrowth.

View full abstract

Serum levels of gentamicin, dibekacin and tobramycin after their signie intramuscular administration at the dose of 100 mg four healthy subjects (avarage body weight 62.5 kg) were pharmacokinetically analyzed with one-compartment open model. There was no significant in the serum levels and in the pharmacokinetic parameters among these three antibiotics.
The serum levels after repetitive intramuscular adminstration of 100 mg per each administration of these antibiotics four times a day (6-hour interval) and three times a day (8-hour interval) were calculated on the basis of the pharmacokinetic parametersobtained from the serum levels after the single intramuscular administration. According to the calculation, the steady state was obtained after the 4 th for 6-hour interval administration, and 3 rd administration for 8-hour interval administration, and the maximal serum concentrations were below 10μg/ml in both cases for the three antibiotics.
Serum dibekacin or tobramycin concentrations were determined during the repetitive intramuscular administration of 100 mg to other threesubjects (avarage body weight 58.2 kg) per each administration. The serum levels were predictedusing the pharmacokinetic parameters calculated from the serum levels after 1 st and 5 th administration. The values predicted were almost thewere almost the same as those observed.
Dibekacin was administered intramuscularly nine times at the dose of 90 mg per each administration at 8-hour interval to a patient (55kg), and gentamicin was adminstred 10 times at the dose of 80 mg per each administration with the same way as dibekacin to another patient 41.5 kg whose Ccr was 46 ml/min. The maximal serum concentrations after st administration were calculated on the basis of the pharmacokinetic parameters obtained from the serum leves lafter 9 th or 10 th administraation. The maximal serum concentrations after 1 st administration of the patients were almost the same as those of the healthy subjects.
Accordingly, the pharmacokinetic analysis of the serum levels after the single administration can provide the prediction of the serum levels afterthe repretitive administration, and also pharmacokinetic analysis of one arbitrary serum level during the repetitive administration can provide the prediction of other serum levels during the repetitive administration.

View full abstract

Serum levels of amikacin and kanamycin were determined after single intramuscular adminsitration at the dose of 400mg and 1, 000mg, respectively, to four healthy subjects. Amikacin was repetitively administered five times at 8-hours interval at the dose of 400mg per each administration to other three healthy subjects, and the serum levels after 1 st and 5 th administration were determined. These serum level were pharmacokinetically analyzed with one-compartment open model. There was no significant difference in pharmacokinetic parameters between amikacin and kanamycin.
The serum amikacin concentrations during the repetitive administration were calculated using the pharmacokinetic parameters obtained from the serum levels after the single administration. The values predicted were almost the same as those observed. The maximal serum concentrations calculated in both single and repetitive administration were below 20μg/ml. On the other hand, the maximal serum concentrations of kanamycin calculated in single and repetitive administration at 12-hour interval were 32.5 and 33.4μg/ml, respectively. They were above 30μg/ml, which has been considered to be a toxic serum concentration of kanamycin.
Renal toxicities in rabbits were compared between amikacin and kanamycin, after these antibiotics were administered, 150mg/kg/day, 300mg/kg/day, and 500mg/kg/day for 10 consecutive days. There was no big difference between two antibiotics, though, amikacin was slightly more toxic than kanamycin.
Accordingly, it is concluded that the twice-a-day use of amikacin at the dose of 400mg are safer clinical therapy than that of kanamycin at the dose of 1, 000mg. Moreover, if the side effects are monitored during the therapy, the three-times-a-day use of amikacin at the dose of 400mg for a serious case are also useful clinical therapy.

View full abstract

The pharmacokinetics of cefotaxime (CTX), a new semi-synthesized cephalosporin antibiotic for injection, was studied in 7 normal volunteers and 23 patients with impaired renal function after a single 1-gram intramuscular injection. Serum and urinary concentrations of CTX and desacetyl CTX were determined by high pressure liquid chromatography. The pharmacomacokinetic parameters of CTX were obtained by analyzing the serum level data of CTX based on a one-compartment open model. The mean peak serum concentrations of CTX and descetyl CTX were 26.3 and 3.2μg/ml in normal subjects, respectively. There was a significant linear correlation (p<0.001) between the elimination rate constant of CTX and the creatinine clearance. The mean serum half-life of CTX was calculated as 52 minutes in normal subjects; the half-life increased in patients parallel with the degree of renal impairment. The mean cumulative urinary recovery of the administred dose in the 24-hour urine was 51.7 per cent as CTX and 25.6 per cent as desacetyl CTX in normal subjects. As renal function declined, the urinary excretion of both CTX and desacetyl CTX decreased.

View full abstract