Comparison of saline vs. blood replenishment after blood sampling in a rat pharmacokinetic study

The objective of this study was to examine the effect of reduced hematocrit and plasma protein levels, which may occur in rats after normal saline replenishment, on the pharmacokinetics of a few model drugs with different RBC (red blood cell) distribution behaviors (i.e., high vs. low). Male Sprague-Dawley rats received either saline or donor blood immediately after each blood sampling following the intravenous administration of model drugs at either 5 or 10 mg/kg. Two drugs with extensive red blood cell distribution, acetazolamide (ACE) and methazolamide (MET), and two additional drugs with negligible RBC distribution, verapamil (VER) and tolbutamide (TOL), were tested. Hematocrit, total plasma protein concentration, and drug concentration were determined after saline or donor blood replenishment. Hematocrit gradually decreased after saline replenishment (30% reduction after 6 h). Consistently, the total plasma protein concentration also decreased after saline replenishment (16% reduction at 6 h). In contrast, hematocrit and total plasma concentration remained unaltered when donor blood was used to replenish the blood volume removed after sampling. Despite the reduction of hematocrit and plasma protein concentration during the course of sampling, the pharmacokinetic profiles of all four drugs tested were similar, regardless of the method of fluid replenishment.