Lack of effect of experimental hypovolemia on imipenem muscle distribution in rats assessed by microdialysis

Abstract

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.

FIG. 1.

Relative recovery by loss of IPM (in percent) in blood and muscle tissue estimated before and after hypovolemia after probe perfusion with IPM solution (10 μg · ml⁻¹) at a flow rate of 2 μl · min⁻¹ in a representative rat.

FIG. 2.

Unbound IPM concentrations in control rats (n = 8) (left panels) and hypovolemic rats (n = 8) (right panels) after a 30-min intravenous infusion of 70 mg · kg⁻¹ of IPM: superimposed mean concentrations in blood (full circles) and muscle tissue (open circles) in control rats (a₁) and hypovolemic rats (a₂), mean ± SD concentrations in blood in control rats (b₁) and hypovolemic rats (b₂), and mean ± SD concentrations in muscle tissue in control (c₁) and hypovolemic rats (c₂).