MEROPENEM CLINICAL PHARMACOKINETICS

Meropenem is a recently developed carbapenem antibiotic, similar to im ipenem, with a wide spectrum of activity against Gram-positive and Gra mnegative bacteria, In comparison with imipenem, meropenem is relative ly stable to hydrolysis by the enzyme dehydropeptidase I (DHP-T), 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 pea k (C-max) of approximately 30 mg/L after administration of a standard dose of Ig intravenously. The elimination half-life (t1/2) is approxim ately 1 hour, and the area under the plasma concentration-time curve i ncreases linearly in a dose-related manner. The volume of distribution is 21L, indicating predominantly extracellular distribution. Meropene m distributes partly into cerebrospinal fluid. The drug is eliminated both by metabolism and excretion. In normal volunteers, up to 70% is r ecovered 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 i s prolonged in patients with renal insufficiency and correlates well w ith creatinine clearance. Dosage adjustments in people with decreased creatinine clearance can, thus, be made on the basis of creatinine cle arance.