cefsulodin and Kidney-Diseases

Seventeen patients with various grades of kidney function were injected each with cefsulodin (CFS) 1 g dissolved in 20 ml of saline. Serum and urine concentrations of CFS were determined using high performance liquid chromatography up to 24 hours after administration. Pharmacokinetic analysis was done using a two-compartment model. The results were discussed by comparing creatinine clearance (Ccr) values divided into 4 groups: greater than or equal to 70 ml/min (group I), 50-less than 70 ml/min (group II), 30-less than 50 ml/min (group III), and less than 30 ml/min (group IV). A delay in the disappearance of CFS from the blood was observed with a decrease in Ccr. Half-lives of CFS in blood (T 1/2 beta) were 1.03 hours (group I), 2.09 hours (group II), 3.44 hours (group III), and 4.52 hours (group IV). Serum clearance (Cls) and Ccr were found to be related with an equation: Cls = 1.60 x Ccr + 7.70. The correlation coefficient (r) was 0.881. Ccr and T 1/2 beta were found to be related with an equation: T 1/2 beta = 31.27 x Ccr-0.688, and the area under the curve (AUC) was found to be related to Ccr with AUC = 4,226 x Ccr-0.81. Urinary excretion rates up to 24 hours after administration were 84.4% (group I), 69.1% (group II), 67.5% (group III), and 56.5% (group IV). This means that CFS is excreted in urine with a relatively high recovery even in the case of low Ccr less than 30 ml/min.

Topics: Cefsulodin; Female; Humans; Injections, Intravenous; Kidney Diseases; Male; Middle Aged

The possible influence of the concomitant administration of cefotiam and cefsulodin on their respective pharmacokinetics was studied in 15 patients with renal insufficiency and 10 anuric patients. Linear relations were found between the clearance of creatinine and the total clearance, as well as the renal clearance, of each drug. These relations for each cephalosporin were not significantly different from previous results obtained after separate administration. In hemodialyzed patients, the two cephalosporins were readily eliminated from the blood after simultaneous administration: ca. 35% of the dose of cefotiam and 30% of the dose of cefsulodin was recovered in the dialysate over 5 h. These results suggest that the pharmacokinetics of the two drugs are not modified by their simultaneous administration and that the dosing schedule previously proposed for administration of the two cephalosporins alone in the presence of renal insufficiency can be applied without modification when they are given together. Patients on hemodialysis should receive a loading dose after each dialysis period, and then reduced doses according to recommendations for anuric patients.

Topics: Adult; Aged; Cefotaxime; Cefotiam; Cefsulodin; Drug Combinations; Female; Humans; Kidney Diseases; Kinetics; Male; Middle Aged; Renal Dialysis

The pharmacokinetics of cefsulodin were characterized in 19 patients with different degrees of renal function after a single 500-mg, 30-min intravenous infusion. Six subjects had a creatinine clearance (Clcr) of greater than 100 ml min-1 (group I), eight had a Clcr of between 12 and 42 ml min-1 (group II), and five had a Clcr of less than 10 ml min-1 (group III). Nine plasma and four urine samples were collected in the first 36 h. The plasma concentration-time data were fitted to a two-compartment open model. The mean beta-phase half-life was 1.77, 6.37, and 10.12 h in groups I, II, and III, respectively. A significant decline in plasma clearance (Clp) was also noted between the three groups: 136 to 49.6 to 27.2 ml min-1 in groups I, II, and III, respectively. Steady-state volume of distribution was 0.26 liter kg-1, regardless of renal function. The observed linear relationship between Clp and Clcr (Clp = 24.09 + 0.765 Clcr; r = 0.9566) can be utilized to revise dosage schedules for patients with any degree of renal impairment. The nonrenal clearance of cefsulodin was also noted to be significantly lower in groups II and III than in group I. Further investigations will be necessary to elucidate the mechanism(s) responsible for the decrease in the nonrenal clearance of cefsulodin.

Topics: Adult; Anti-Bacterial Agents; Cefsulodin; Cephalosporins; Creatinine; Female; Humans; Kidney Diseases; Kinetics; Male; Metabolic Clearance Rate; Middle Aged

Cefsulodin kinetics were determined after a 500-mg dose to normal subjects and patients with varying degrees of renal insufficiency, including those requiring hemodialysis. Elimination kinetics were described by a two-compartment model. Steady-state volume of distribution was 0.26 l/kg regardless of renal function. When glomerular filtration rate (GFR) was more than 80 ml/min, elimination half-life (t1/2) was 1.9 hr, total body clearance (ClT) was 2.01 ml/kg/min, and renal clearance (ClR) was 1.09 ml/kg/ in. When GFR ranged from 79 to 53 ml/min, t1/2 was 2.9 hr, ClT was 1.17 ml/kg/min, and ClR was 0.65 ml/kg/min. In subjects with moderate renal failure in whom GFR was 32 to 22 ml/min, t1/2 was 5.7 hr, Clt was 0.66 ml/kg/min, and ClR was 0.26 ml/kg/min. In anuric patients t1/2 was 13.0 hr. and ClT was 0.19 ml/kg/min or 9.5% of ClT in normal subjects. There was a linear relationship between ClT and GFR such that ClT = 0.19 + 0.017 GFR (r = 0.95). During hemodialysis the average plasma flow was 122 ml/min, dialyzer plasma clearance was 50.9 ml/min, plasma drug concentration was reduced by 60%, and t1/2 fell to 2.1 hr. After dialysis the elimination rate appeared to return to that in nondialysis studies. Therefore, renal failure reduces the ClT of cefsulodin. In hemodialysis patients the maintenance dose of cefsulodin should be reduced to 10% of normal and 60% of the dose should be given after hemodialysis.

Topics: Adult; Cefsulodin; Cephalosporins; Creatinine; Female; Glomerular Filtration Rate; Humans; Injections, Intravenous; Kidney Diseases; Kinetics; Male; Renal Dialysis