The pharmacokinetics of meropenem.

Abstract

Meropenem is a new carbapenem antibiotic which differs chemically from imipenem/cilastatin by having a 1-beta-methyl substitution, providing it with excellent intrinsic stability to human renal dehydropeptidase-I. In addition, an altered 2' side chain enhances its anti-pseudomonal activity. The drug has one identified metabolite, a beta-lactam ring-opened form which is devoid of microbiological activity, as would be expected. The parent compound displays linear pharmacokinetics over a dose range of 250 mg to 2 g. The terminal half-life is approximately 1 hour and the plasma clearance is approximately 15.5 L/h/70 kg. The plasma concentrations after a 1 g dose show a trough concentration (8 hours) of slightly greater than 0.25 mg/L. The renal route is the major clearance pathway for this drug and its metabolite, with renal clearance accounting for approximately 70% of the plasma clearance and there being approximately 70% of an administered dose recovered in the urine as intact parent compound over 12 hours. When combined with metabolite, over 90% of administered radiolabel is recovered in the urine over this 12 hour period. As expected, renal functional impairment alters the clearance of meropenem, but the alteration is predictable. Hepatic functional impairment does not alter drug disposition and no dosing alterations are required here. In summary, meropenem's disposition is similar to that seen for imipenem/cilastatin, except that no renal dehydropeptidase-I inhibitor is required. When evaluated against the background of its excellent profile of in vitro activity, it is clear that this is a drug of great promise which should be extensively evaluated in clinical trials of seriously ill patients with nosocomial infections.