Pharmacokinetics of cefodizime in patients with liver cirrhosis and ascites

Abstract

The pharmacokinetics of cefodizime were studied in 6 healthy male volunteers (group A) and 6 patients with liver cirrhosis and ascites (group B) receiving 1 g of the drug as an i.v. bolus. Cefodizime was assayed in serum and ascitic fluid (AF) samples by a microbiological assay. The serum concentration-time curve fitted a two-compartment open model in group A and a three-compartment open model in group B. Initially, the serum level of cefodizime in group A exceeded that in group B for about 10 h; thereafter the reverse occurred until 24 h post-dosing. Cefodizime penetrated rapidly into the AF, reaching a peak at 6 h, and its AF level was still above the MIC90 for Enterobacteriaceae in most patients at 24 h post-dosing. The half-life of distribution did not differ significantly between the two groups, while the elimination half-life was prolonged significantly (p < 0.001) from 2.7 +/- 0.2 h in group A to 5.4 +/- 0.8 h in group B. The central volume of distribution (Vc) did not differ significantly in the two groups, while the terminal volume of distribution (Vp) was significantly smaller (p < 0.01) in group A (0.172 +/- 0.30 l/kg) than in group B (0.55 +/- 0.20 l/kg). The area under the serum concentration-time curve (AUC0-infinity serum) was significantly larger (p < 0.001) in group A [322 +/- 34 (micrograms/ml).h than in group B (180 +/- 34 (micrograms/ml).h]. The area under the AF concentration-time curve (AUC0-infinity ascites) in group B was 141 +/- 37 (micrograms/ml).h.(ABSTRACT TRUNCATED AT 250 WORDS)