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Antimicrobial Agents and Chemotherapy, December 2005, p. 4974-4979, Vol. 49, No. 12
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.12.4974-4979.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Lack of Effect of Experimental Hypovolemia on Imipenem Muscle Distribution in Rats Assessed by Microdialysis

EA 3809, Faculté de Médecine et de Pharmacie, BP 199, 34 rue du Jardin des Plantes, 86005 Poitiers Cedex, France,¹ Laboratoire de Pharmacocinétique, PBS, CHU La Milétrie, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France,² Département d'Anesthésie et Réanimation Chirurgicale, CHU La Milétrie, 86021 Poitiers, France³

Received 5 July 2005/ Returned for modification 22 August 2005/ Accepted 1 September 2005

The aim of this study was to investigate the influence of hypovolemia on the distribution of imipenem in muscle extracellular fluid determined by microdialysis in awake rats. Microdialysis probes were inserted into the jugular vein and hind leg muscle. Imipenem recoveries in muscle and blood were determined in each rat by retrodialysis by drug before drug administration. Hypovolemia was induced by removing 40% of the initial blood volume over 30 min. Imipenem was infused intravenously at a dose of 70 mg · kg^–1 over 30 min, and microdialysis samples were collected for 120 min from hypovolemic (n = 8) and control (n = 8) rats. The decay of the free concentrations in blood and muscle with time were monoexponential, and the concentration profiles in muscle and blood were virtually superimposed in both groups. Accordingly, the ratios of the area under the concentration-time curve (AUC) for tissue (muscle) to the AUC for blood were always virtually equal to 1. Hypovolemia induced a 23% decrease in the clearance (P < 0.05) of imipenem, with no statistically significant alteration of its volume of distribution. This study showed that imipenem elimination was altered in hypovolemic rats, probably due to decreased renal blood flow, but its distribution characteristics were not. In particular, free imipenem concentrations in blood and muscle were always virtually identical.

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