Pharmacokinetics of imipenem and cilastatin in volunteers

Imipenem/cilastatin sodium consists of imipenem, a broad-spectrum carbapenem antimicrobial agent, and cilastatin sodium, an inhibitor of dehydropeptidase I, the renal enzyme that catalyzes the metabolism of imipenem. When imipenem is administered alone by the intravenous route, the levels excreted in the urine are low and variable (6%-38% of the dose) between subjects. Kinetics of imipenem in plasma are less variable, and the half-life of imipenem in plasma is 1 hr. When imipenem is coadministered with an equal amount of cilastatin, the amount of imipenem excreted in the urine represents 70% of the plasma clearance and the plasma half-life remains at 1 hr. Whether administered alone or with imipenem, the urinary excretion of cilastatin is 70%-80% of the dose administered, and its plasma half-life is also 1 hr. Thus, the pharmacokinetics of both agents are linear across the therapeutic dose range, and no accumulation of these agents occurs for therapeutic regimens. Decreases in renal function slow the elimination of both compounds and require a reduction in dosage when the glomerular filtration rate is less than 30 ml/min per 1.73 m2.