Pharmacokinetics of Cefotaxime and Desacetylcefotaxime in Patients with Liver Disease

The dispositions of cefotaxime and its metabolite desacetylcefotaxime were investigated in patients with different forms of chronic parenchymal liver disease (CPLD). A total of 31 subjects (27 patients and 4 controls) received a single 2-g dose of cefotaxime by infusion, and serial blood samples were drawn. The area under the concentration-time curve ranged from 176 to 241,ug h/ml, the apparent half-life ranged from 1.49 to 2.42 h, and clearance ranged from 2.06 to 3.10 ml/min/kg in patients with four different forms of CPLD. The area under the concentration-time curve and the apparent half-life of desacetylcefotaxime ranged from 72 to 128 jig h/ml and 7.1 to 13.4 h, respectively. Pharmacokinetic parameters were significantly different in patients with CPLD compared with those in control subjects and were related to clinical indices of hepatic impairment. Modest accumulation of cefotaxime in patients with severe hepatic impairment is unlikely to produce toxicity because of its high therapeutic index, and dosing modifications may not be required. Cefotaxime (Claforan; Hoechst-Roussel Pharmaceuticals, Inc., Somerville, N.J.), an expanded-spectrum cephalospo-rin, has a broad spectrum of antibacterial activity against aerobic cocci and enteric gram-negative bacilli. Cefotaxime is normally cleared by both renal excretion and hepati