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Antimicrobial Agents and Chemotherapy, June 2005, p. 2356-2361, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2356-2361.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Microdialysis Study of Imipenem Distribution in Skeletal Muscle and Lung Extracellular Fluids of Noninfected Rats

Sandrine Marchand,1,2,{dagger} Claire Dahyot,3,{dagger} Isabelle Lamarche,1 Olivier Mimoz,1,3 and William Couet1,2*

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 2 September 2004/ Returned for modification 30 October 2004/ Accepted 14 February 2005

The aim of this study was to investigate the imipenem distribution in muscle and lung interstitial fluids by microdialysis in rats and to compare the free concentrations in tissue with the free concentrations in blood. Microdialysis probes were inserted into the jugular vein, hind leg muscle, and lung. Imipenem recoveries in these three media were determined in each rat by retrodialysis by drug period before drug administration. Imipenem was infused intravenously at a dose of 120 mg · kg–1 over 30 min, and microdialysis samples were collected for 150 min. The whole study was conducted with nonhydrated rats (n = 4) and hydrated rats (n = 6) while the animals were under isoflurane anesthesia. The decay of free concentrations in blood, muscle, and lung with time were monoexponential; and the concentration profiles in these three media were virtually superimposed in both groups. Accordingly, the ratios of the area under the curve (AUC) for tissue (muscle or lung) to the AUC for blood were always virtually equal to 1. Compared to values previously determined with awake rats, clearance was reduced by 2 and 1.5 in nonhydrated and hydrated rats, respectively, but the volume of distribution was unchanged. By combining microdialysis in blood and tissues, it was possible to demonstrate that free imipenem concentrations were virtually identical in blood, muscle, and lung.

* Corresponding author. Mailing address: EA 3809, Pôle Biologie Santé (PBS), Médecine-Sud, Niveau 1, 40 Avenue du Recteur Pineau, 86022 Poitiers Cedex, France. Phone: 33-5-49-45-43-79. Fax: 33-5-49-45-43-78. E-mail: william.couet{at}univ-poitiers.fr.

{dagger} C.D. and S.M. contributed equally to this paper.

Antimicrobial Agents and Chemotherapy, June 2005, p. 2356-2361, Vol. 49, No. 6
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.6.2356-2361.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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