Effect of experimentally induced hypovolemia on ertapenem tissue distribution using microdialysis in rats

Hypovolemia is a common event in critical care patients that may affect drug distribution and elimination. In order to better understand this issue the effect of hypovolemia on the plasma protein binding and tissue distribution of ertapenem was investigated in rats using microdialysis. Microdialysis probes were inserted into the jugular vein and hind leg muscle. Ertapenem recoveries in muscle and blood were determined in each rat by retrodialysis by drug before drug administration. Hypovolemia was induced in 6 rats by removing 40% of the initial blood volume over 30 min. Ertapenem was infused intravenously at a dose of 40 mg kg(-1) over 30 min, and microdialysis samples were collected for 310 min. The unbound concentration profiles in muscle and blood were virtually superimposed in both groups except at early time points. The ratios of the area under the concentration-time curve (AUC) for tissue to the AUC for blood were 0.7±0.2 and 0.8±0.2 for control and hypovolemic rats, respectively. Hypovolemia induced a 40% decrease in the clearance of ertapenem, with no statistically significant alteration of its volume of distribution. This study showed that ertapenem elimination was altered in hypovolemic rats, probably due to decreased renal blood flow, but its distribution characteristics were not. Unbound concentrations of ertapenem in blood and muscle were always virtually identical.