Pharmacokinetics of cefotaxime in patients after liver transplantation

The pharmacokinetics of cefotaxime including formation of its active metabolite desacetyl-cefotaxime were assessed after liver transplantation in three groups of patients (four patients per group): --during the postoperative recovery phase (group 1), --during an episode of allograft nonfunction (group 2), --during an episode of allograft rejection (group 3). All patients received a single dose of 1 g cefotaxime intravenously. Concentrations of cefotaxime and its metabolite were determined in plasma and urine until 6 to 72 h after medication. The terminal half-life of cefotaxime increased and total clearance decreased due to an impairment of drug metabolism, mainly in patients with a nonfunctioning allograft and during rejection. Thus, no desacetyl-cefotaxime was detectable in urine of any patient and none in plasma of 2/4 patients with a nonfunctioning allograft. In addition, a moderate impairment of renal function in several patients contributed to the delayed elimination of cefotaxime and its metabolite. It can be concluded that liver function after transplantation is correlated with the ability to eliminate cefotaxime. Therefore, administration of half the normal dose is recommended particularly in patients with a nonfunctioning allograft or during rejection.