Clinical pharmacokinetics of cefotetan.

Cefotetan is a 7-alpha-methoxy beta-lactam. A long serum half-life and resistance to beta-lactamase hydrolysis have made cefotetan an attractive chemotherapeutic agent, and the results of clinical trials worldwide have demonstrated its efficacy in a wide variety of clinical situations. Cefotetan can be administered intravenously (bolus or infusion) or intramuscularly with lidocaine (lignocaine) 0.5%. Mean peak plasma concentrations are almost linearly related to dose. The volume of distribution is between 8 and 13L and is not different from other cephalosporins. No accumulation is seen after repeated doses and no metabolite has been detected in either plasma or urine. Total body clearance is 1.8 to 2.9 L/h. Renal clearance accounts for about 64 to 84% of a dose, and 75% of a dose is excreted in the urine within 24 hours. The plasma elimination half-life is between 3 and 4 hours after intravenous and intramuscular doses. Half-life is considerably prolonged in patients with renal impairment (up to 10 hours). Cefotetan concentrations are likely to be active against susceptible bacteria in most tissues and body fluids. Breast milk and cerebrospinal fluid concentrations are low. The recommended dosage is 1g every 12 hours, increasing to 2g in severe infections and 3g in life-threatening infections. In surgical prophylaxis, a single dose of 2g is given with the induction of anaesthesia; an additional dose of 2g may be administered 12 hours later. In children over 6 months, the recommended dosage is 30 mg/kg given 12-hourly. In patients with a creatinine clearance of 10 to 40 ml/min (0.6 to 2.4 L/h), the dose is halved or the dosage interval is doubled. When creatinine clearance is less than 10 ml/min (0.6 L/h), the dose is quartered or the dosage interval quadrupled.