Pharmacokinetics of imipenem in serum and skin window fluid in healthy adults after intramuscular or intravenous administration

Abstract

The pharmacokinetic profiles of imipenem after intramuscular (i.m.) and intravenous injections were examined in adult volunteers. Levels of imipenem in serum after i.m. injection of a microcrystalline suspension of imipenem-cilastatin (500 mg each) reached a peak (8.0 micrograms/ml) at 1.5 h after administration, and concentrations were maintained in excess of 1.5 micrograms/ml for 6 h. Serum elimination half-life (1.3 h), volume of distribution (14.5 liters), and area under the curve (AUC; 27.8 micrograms.h/ml) after i.m. injection did not significantly differ from those of a comparable dose given by intravenous infusion. Bioavailability after i.m. injection was 89%. Imipenem levels in skin window fluid after i.m. administration were maximal (4.3 micrograms/ml) at 4 h after injection, at which time imipenem concentrations exceeded those produced by intravenous infusion. The AUCskin window/AUCserum ratio for skin window fluid after i.m. injection was 68%, indicating good penetration of the drug into skin fluid. This study shows that i.m. injection of 500 mg of imipenem-cilastatin results in concentrations of imipenem in serum and skin fluid that are, for at least 6 h, consistent with antimicrobial activity against susceptible organisms.