Pharmacokinetics of cefotetan in normal subjects and patients with impaired renal function.
The elimination kinetics of cefotetan (YM09330), a new parenteral semisynthetic cephamycin derivative, were studied in eight healthy volunteers and 41 patients with renal insufficiency after the administration of a single 500-mg dose intravenously. Concentrations of cefotetan in serum and urine were determined by both bioassay and high-pressure liquid chromatography. The pharmacokinetic parameters for cefotetan were calculated on the basis of a two-compartment open model. Serum concentrations of cefotetan immediately after administration were approximately 180 micrograms/ml in all subjects regardless of function; however, serum concentrations during the beta-phase increased directly with the degree of renal impairment. The mean serum half-life during the beta-phase was 3.0 h in normal subjects as compared with 13.1 h in hemodialysis patients. There was a linear correlation (P less than 0.0001) between the elimination rate constant of cefotetan and creatinine clearance. The mean cumulative urinary recovery of cefotetan in the 24-h urine was 83.3% of the administered dose in normal subjects and decreased with reduced renal function.
D000328:Adult; D000368:Aged; D015313:Cefotetan; D002511:Cephalosporins / Q000378:metabolism*; D002513:Cephamycins / Q000378:metabolism*; D003404:Creatinine / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007674:Kidney Diseases / Q000378:metabolism*; D007700:Kinetics; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D006435:Renal Dialysis
D002511:Cephalosporins; D002513:Cephamycins; D015313:Cefotetan; D003404:Creatinine