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. 2005 Jun;49(6):2356-61.
doi: 10.1128/AAC.49.6.2356-2361.2005.

Microdialysis study of imipenem distribution in skeletal muscle and lung extracellular fluids of noninfected rats

Sandrine Marchand  1 , Claire Dahyot, Isabelle Lamarche, Olivier Mimoz, William Couet
Affiliations

Microdialysis study of imipenem distribution in skeletal muscle and lung extracellular fluids of noninfected rats

Sandrine Marchand et al. Antimicrob Agents Chemother. 2005 Jun.

Abstract

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.

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Figures

FIG. 1.
FIG. 1.
Relative recovery by loss of imipenem (%) in blood, muscle, and lung in a representative rat obtained after probe perfusion with imipenem solution (10 μg · ml−1) at a flow rate of 1 μl · min−1 for 150 min.
FIG. 2.
FIG. 2.
Unbound imipenem concentrations in nonhydrated rats (n = 4) after a 30-min intravenous infusion of 120 mg · kg−1 of imipenem: superimposed mean concentrations in the three media (blood, muscle, and lung) (a), mean ± SD concentrations in blood (b), mean ± SD concentrations in muscle (c), and mean ± SD concentrations in lung (d).
FIG. 3.
FIG. 3.
Unbound imipenem concentrations in hydrated rats (n = 6) after a 30-min intravenous infusion of 120 mg · kg−1 of imipenem: superimposed mean concentrations in the three media (blood, muscle, and lung) (a), mean ± SD concentrations in blood (b), mean ± SD concentrations in muscle (c), and mean ± SD concentrations in lung (d).
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