Pharmacokinetics of Cefoperazone

The pharmacokinetics of cefoperazone in normal subjects, and in patients with hepatic and renal dysfunction are reviewed. After intravenous administration of 2g of cefoperazone, levels in serum ranged from 202 to 375µg/ml depending on the period of drug administration. After intramuscular injection of 2g of cefoperazone, the mean peak serum level was 11 1µg/ml at 1.5 hours. At 12 hours after dosing, mean serum levels were still 2 to 4µg/ml. Cefoperazone was 90% bound to serum proteins. The apparent volume of distribution was 10 to 13L. The half-life of the drug varied from 1.6 to 2.4 hours; serum clearance was between 75 and 96ml/min. Urinary excretion was rapid, but only 15 to 36 % of the cefoperazone dose was recovered in the urine. Renal clearance ranged from 14 to 25ml/min. Urine levels of cefoperazone in excess of 32µg/ml were maintained for at least 12 hours. Biliary levels of cefoperazone were many-fold higher than serum levels; peak bile concentrations from 675 to 6000µg/ml were obtained. Severe hepatic dysfunction was associated with a 2- to 4-fold increase in the half-life of cefoperazone. In patients with relatively complete biliary obstruction, over 90 % of the dose was recovered in the urine. In contrast, the serum kinetics of cefoperazone were not significantly altered in patients with renal impairment. The human pharmacology of cefoperazone is similar to cephazolin in terms of serum concentrations, half-life, protein binding, and apparent volume of distribution, but markedly different in terms of biliary and renal excretion. Since biliary excretion is normally the primary route of cefoperazone elimination, dosage modification should only be required in the presence of severe biliary obstruction or concomitant renal and hepatic dysfunction.