Clinical pharmacokinetics of cefotaxime in patients with normal and reduced renal function

Two analytic methods for measuring cefotaxime, microbiologic and high-pressure liquid chromatography (HPLC), were compared in normal healthy subjects and in patients with impaired renal function. Results of studies showed that in healthy subjects the levels of desacetylcefotaxime are low relative to those of cefotaxime and that either a bioassay or HPLC is adequately specific for determination of pharmacokinetic parameters. However, in patients with decreased renal function, desacetylcefotaxime reaches much higher levels than in healthy subjects. Thus, the less specific bioassay produces misleading data on serum and urine concentrations in these patients, and the HPLC assay of cefotaxime is recommended for estimating pharmacokinetic parameters in patients with decreased renal function. In healthy subjects and in patients with a creatinine clearance greater than 20 ml/min, neither cefotaxime nor its metabolites accumulates after multiple dosing. If creatinine clearance is less than 20 ml/min, metabolites begin to accumulate. It is recommended that until further data are obtained the dose of cefotaxime given to patients with an estimated creatinine clearance of less than 20 ml/min be half that given to patients with values greater than 20 ml/min.