Single and multiple dose pharmacokinetics of intravenous cefpirome (HR 810), a novel cephalosporin derivative.

Abstract

After intravenous injection of single doses of 1.0 g of cefpirome (HR 810) and multiple doses of 1.0 g b.i.d. for five days to the same ten healthy male volunteers in an open design, concentrations of unchanged drug were estimated at various times in serum and urine, over 24 h and 48 h, respectively. Cefpirome concentrations were determined using both high pressure liquid chromatography (HPLC) and a microbiological assay. The measurements obtained were compared by linear distribution independent regression, and were found to be equivalent, indicating no major antimicrobially active metabolites of cefpirome. Biological half-life (t1/2,beta) was determined by fitting a two-compartment open model to the data: t1/2,beta was 2 h (HPLC, median values). During the multiple dose phase of cefpirome (1.0 g b.i.d.) no accumulation of the serum levels could be detected with this dosage regimen. Urinary concentrations of unchanged cefpirome remained clearly above the minimal inhibitory concentration for Escherichia coli (0.03 mg/l) for about 36 h (microbiological assay). The general tolerance was good.