Cefoperazone is a new piperazine cephalosporin derivative which has a broad antibacterial activity against aerobic and anaerobic gram-positive and gram-negative cocci and bacilli, includingPseudomonas aeruginosa.In studies of the intramuscular (i.m.) administration of cefoperazone at doses of 0.25, 0.5, and 1 g, mean peak serum concentrations were 22, 33, and 67 μg/ml at 1 hr. At 8 hr, serum levels were 2.1, 4.8, and 5.6μg/ml, respectively, for the three doses. The mean half-life after intramuscular injection was 108–154 min. Urinary recovery ranged from 14 to 18% of an administered dose. Intravenous (i.v.) administration of cefoperazone by rapid (3–5 min) infusion produced serum levels at 15 min of 76, 156, and 244 μg/ml after doses of 0.5, 1, and 2 g, respectively. Concentrations of cefoperazone at 8 hr were 2.4, 6.5, and 11.8 μg/ml after these respective doses. Serum half-life was 115–120 min and urinary recovery, 29–33%. Levels determined at 5 min after bolus injection were 200 μg/ml for 1 g, 275 μg/ml for 2 g and 518 μg/ml for 3 g. Intravenous infusion studies of cefoperazone in which 2 g of the drug has been infused over 15, 30, or 120 min have yielded levels of 250–260 μg/ml. At 12 hr, levels of 1–2 μg/ml were still present. The half-life found in these studies ranged from 1.6 to 2.38 hr Urinary recovery was 25–30%. Serum clearances have been 80–90 ml/min and renal clearances, 18–30 ml/min. The apparent volume of distribution of the compound has ranged from 10 to 16 liters. Comparative studies have shown that cefoperazone produced higher serum levels than cefazolin, cefamandole, cefotaxime, and moxalactam. Biliary concentrations exceed 400 μg/ml and are two to four times the levels found with cefazolin or cefamandole. In the presence of renal failure there is a minimal increase in serum half-life; but in the presence of biliary obstruction, serum half-life may reach 11 hr, depending on the degree of biliary obstruction. In the presence of biliary obstruction, the drug is 90% removed from the body by renal excretion.