[Pharmacokinetics of cefotaxime in patients with chronic renal impairment (author's transl)]

Abstract

The pharmacokinetics of cefotaxime were investigated in 6 healthy subjects and in 22 uraemic patients with various degrees of renal insufficiency. After i.v. bolus injection of a single 15 mg/kg dose, pharmacokinetic data were calculated using a two compartment model. Serum and urine concentrations were determined by microbiological (M.A.) and HPLC assays. With microbiological assay, the elimination serum half-life (T 1/2) increased in patients according to their degree of renal insufficiency and reached 10 hours when creatinine clearance fell below 10 ml.min-1. When concentrations of cefotaxime and its derivatives (desacetyl cefotaxime, M2 and M3) were determined by HPLC assay, the elimination serum half-life of cefotaxime (T 1/2) was not modified in severe uraemic patients; however the elimination half-life of the metabolites increased when creatinine clearance decreased. Cefotaxime can be administered at a dose of 1 g i.v., twice daily in patients with stable chronic renal insufficiency when creatinine clearance is above 5 ml min-1. In cases of more severe renal failure, the dose should be halved and given i.v. every 12 hours.