Kyoichi Kuroda

Elimination Kinetics of Cefotaxime and Desacetyl Cefotaxime in Patients with Renal Insufficiency and during Hemodialysis

The pharmacokinetics of cefotaxime, a new semi-synthetic cephalosporin for injection, was studied in 30 subjects with various degrees of renal function after a single 1-gram intramuscular injection. Serum and urinary concentrations of cefotaxime and desacetyl cefotaxime were determined by high pressure liquid chromatography. The pharmacokinetic parameters of cefotaxime were obtained using a one-compartment open model. The mean serum half-life of the parent compound (cefotaxime), 0.87 h in normal subjects, was prolonged to 2.35 h in hemodialysis patients. There was a significant linear correlation between the elimination rate constant of cefotaxime and creatinine clearance. The mean cumulative urinary recovery of the administered dose in the 24-hour urine was 51.7% as cefotaxime and 25.6% as desacetyl cefotaxime in normal subjects.

Anticancer drug sensitivity in vitro in the bladder cancer cell line, KK-47 and prophylactic use of carbazilquinone and urokinase in bladder cancer.

SummaryUsing colony formation technique and KK-47 cell line established from a human bladder transitional cell carcinoma, the effects of 6 anticancer drugs, thio-TEPA, Bleomycin, mitomycin C, carbazilquinone, Adriamycin and cis-Platinum, were compared. On the results of tests performed to establish the drug concentration required to achive a 50% inhibition of cell survival, carbazilquinone was chosen for the prevention of recurrences of bladder cancer. The two groups studied consisted of 56 patients (previously untreated group) who were rendered free of tumours by surgical intervention and of 19 patients (thio-TEPA failures group) who had experienced a persistent recurrence of tumours after prophylactic thio-TEPA instillations and were presumed free of the recurrence of tumours after the next surgical intervention. The 2 groups were subjected to prophylactic combined intravesical instillation therapy with carbazilquinone and urokinase. In the previously untreated group, 6 of the 56 patients (10. 7%) had a recurrence of tumours, and the recurrence rate after 21 months was 16. 7%, using the actuarial method. In the thio-TEPA failures group, 12 of the 19 patients (63. 2%) had a recurrence of tumours, a rate at 21 months of 76. 1%. A considerable drop in the recurrence rate was obtained by the combined instillation therapy in the previously untreated group. The results in the thio-TEPA failures group suggested the presence of a cross-resistance between both alkylating agents, and of a persistent susceptibility to multifocal lesions. No bone marrow depression was observed but an episode of anaphylactic shock attributable to the use of carbazilquinone occurred in 1 out of a total 75 patients.

Pharmacokinetics of Cefroxadine in Healthy Volunteers and Patients with Impaired Renal Function

The pharmacokinetics of cefroxadine, a new orally active broad-spectrum cephalosporin, was studied in healthy volunteers and patients with impaired renal function after a single oral dose of 500 mg. The pharmacokinetic parameters of cefroxadine were obtained by analysing the serum level data of the drug based on a one-compartment open model. The mean serum half-life of cefroxadine was 0.97 h in healthy subjects, and was prolonged to 41.7 h in patients with a creatinine clearance of less than 5 ml/min. There was a significant linear correlation (p less than 0.001) between the elimination rate constant of the drug and the creatinine clearance. In healthy subjects, 71% of the administered dose was excreted in the urine collected over the first 6 h.

Pharmacokinetics of Ceftezole in Patients with Normal and Impaired Renal Function

The pharmacokinetics of ceftezole, a new cephalosporin antibiotic, was studied in 15 patients with normal and impaired renal function after administering the drug in a 2-hour intravenous drip infusion of 2 g. 81% of the infused dose was excreted in the first 6 h urine of the patients with normal renal function. The pharmacokinetic parameters of ceftezole were obtained by analyzing the serum level data of the drug using a one-compartment open model. The mean serum half-life of ceftezole was 0.64 h in patients with normal renal function and was prolonged to 10.7 h in patients with severely impaired renal function (creatinine clearance: 0-2.6 ml/min.). There was a significant linear correlation between the elimination rate of the drug and creatinine clearance.