Pharmacokinetics of imipenem in dogs

Abstract

Objective - To determine the plasma pharmacokinetics of imipenem (5 mg/kg) after single-dose IV, IM, and SC administrations in dogs and assess the ability of plasma samples to inhibit the growth of Escherichia coli in vitro. Animals - 6 adult dogs. Procedure - A 3-way crossover design was used. Plasma concentrations of imipenem were measured after IV, IM, and SC administration by use of high-performance liquid chromatography. An agar well antimicrobial assay was performed with 3 E coli isolates that included a reference strain and 2 multidrug-resistant clinical isolates. Results - Plasma concentrations of imipenem remained above the reported minimum inhibitory concentration for E coli (0.06 to 0.25 μg/mL) for a minimum of 4 hours after IV, IM, and SC injections. Harmonic mean and pseudo-standard deviation half-life of imipenem was 0.80 ± 0.23, 0.92 ± 0.33, and 1.54 ± 1.02 hours after IV, IM, and SC administration, respectively. Maximum plasma concentrations (Cmax) of imipenem after IM and SC administration were 13.2 ± 4.06 and 8.8 ± 1.7 mg/L, respectively. Time elapsed from drug administration until Cmax was 0.50 ± 0.16 hours after IM and 0.83 ± 0.13 hours after SC injection. Growth of all 3 E coli isolates was inhibited in the agar well antimicrobial assay for 2 hours after imipenem administration by all routes. Conclusions and Clinical Relevance - Imipenem is rapidly and completely absorbed from intramuscular and subcutaneous tissues and effectively inhibits in vitro growth of certain multidrug-resistant clinical isolates of E coli.