Meropenem clinical pharmacokinetics

Abstract

Meropenem is a recently developed carbapenem antibiotic, similar to imipenem, with a wide spectrum of activity against Gram-positive and Gram-negative bacteria. In comparison with imipenem, meropenem is relatively stable to hydrolysis by the enzyme dehydropeptidase I (DHP-I), thus precluding the need for coadministration with an inhibitor of DHP-I, such as cilastatin. Furthermore, meropenem may be less nephrotoxic and neurotoxic than imipenem. Plasma meropenem concentrations reach a peak (Cmax) of approximately 30 mg/L after administration of a standard dose of 1 g intravenously. The elimination half-life (t1/2) is approximately 1 hour, and the area under the plasma concentration-time curve increases linearly in a dose-related manner. The volume of distribution is 21L, indicating predominantly extracellular distribution. Meropenem distributes partly into cerebrospinal fluid. The drug is eliminated both by metabolism and excretion. In normal volunteers, up to 70% is recovered in urine, and the remainder is accounted for by a beta-lactam ring-opened form of the compound, ICI 213689. The t1/2 of meropenem is prolonged in patients with renal insufficiency and correlates well with creatinine clearance. Dosage adjustments in people with decreased creatinine clearance can, thus, be made on the basis of creatinine clearance.