Pharmacokinetics of cefpirome (HR 810), a new cephalosporin derivative administered intramuscularly and intravenously to healthy volunteers

Abstract

The pharmacokinetics of cefpirome (HR 810)3-(2,3-cyclopenteno-1-pyridinium)-methyl-7-2-synmethoximino -2-(2- aminothiazol-4-yl)-acetamido-ceph-3-em-4-carboxylate, a new cephalosporin with an extremely broad antimicrobial spectrum, were tested in an open cross-over trial in ten healthy male volunteers using i.v. and i.m. injections of 1 g. Serum concentrations were monitored over 24 h after application, using both chromatographic and microbiological assays. Urine was collected in 2-h fractions for up to 8 h after application, then for 4 h, and thereafter in 12-h fractions for up to 48 h after application. Urine concentrations of the drug were measured by both HPLC and bioassay. The measurements were compared by linear distribution independent regression, and were found to be equivalent, indicating no major antimicrobially active metabolites of HR 810. A two-compartment open model was used for the calculation of pharmacokinetic parameters for both i.v. and i.m. dosing. The median maximum concentration in plasma after i.m. administration was 30.6 mg/l at 1.6 h (HPLC). The elimination half-life times of 1.9 h to 2.1 h did not differ significantly between the two routes investigated. With regard to bioavailability there was no difference between the i.m. and i.v. routes, as demonstrated by the AUC and urinary recovery of unchanged substance. Clinically relevant urine concentrations of cefpirome were detected for at least 12 h after dosing. The general tolerability was good.