Pharmacokinetics of cefoperazone in patients with normal and impaired hepatic and renal function

The pharmacokinetics of cefoperazone in normal subjects and in patients with hepatic and renal dysfunction are reviewed. Peak serum concentrations and areas under serum level-time curves are linearly related to dose. The range of mean peak serum concentrations after a 2-g dose of cefoperazone is 202-375 micrograms/ml with iv injection or infusion and 111 micrograms/ml with im injection. The serum half-life is 1.6-2.6 hr. Urinary excretion is rapid, but only 15%-37% of the dose is recovered in urine. The drug is not metabolized significantly. Levels of drug in bile are many times higher than serum levels, and biliary excretion represents the major pathway of cefoperazone elimination. Serum kinetics of cefoperazone are not significantly altered by renal impairment. However, hepatic dysfunction is associated with a two- to fourfold increase in serum half-life. Even in these patients, drug accumulation was not observed after repeated administration of 1 g of cefoperazone at 12-hr intervals. Major dosage modification should only be required with concomitant renal and hepatic dysfunction.