Serum levels and urinary excretion of cefoperazone in patients with hepatic insufficiency

The pharmacokinetics of cefoperazone, a new cephalosporin with a spectrum extended to includePseudomonas aeruginosa, Enterobacter cloacae andSerratia marcescens, were studied after a 2 h intravenous infusion of 2 g in six patients with impaired liver function. This was due to viral hepatitis in four cases and to alcoholic fatty liver and cirrhosis in two. Eight healthy volunteers with normal liver function constituted the control group. At the end of the infusion, mean serum concentrations (determined by bioassay usingSarcina lutea) were 208 mg/l in patients with hepatic disease and 134 mg/l in volunteers. The apparent half-life of elimination was significantly prolonged in patients (4.3 h), compared with volunteers (1.6 h). Total clearance, which averaged 77.7 ml/min in volunteers, was significantly reduced in patients (32.5 ml/min). Renal clearance was similar in the two groups (25.5 ml/min in patients and 18.3 ml/min in volunteers) but the extrarenal clearance of cefoperazone was significantly lower in the patients (7.3 ml/min) than in the control group (59.4 ml/min). There was no difference between the groups with regard to the volume of distribution. Urinary excretion of biologically active drug was significantly increased in patients (Ae∞=1580 mg) compared with volunteers (Ae∞=470 mg). This study provides evidence that impaired liver function increases both the apparent half-life of elimination and urinary excretion of the drug. Our results raise the question of adjusting the dosage of cefoperazone in patients with hepatic disease.