BUPIVACAINE KINETICS DURING HYPERTHERMIA IN RATS

The aim of this study was to document possible alterations of bupivaca ine pharmacokinetic behaviour in rats during hyperthermia. Two groups of Wistar AF IOPS male rats (Group A = normothermic controls, Group B = hyperthermia-induced animals) received a single 20 mg.kg(-1) ip dose of bupivacaine. Two other groups (Group C = normothermic controls wit hout bupivacaine, Group D = hyperthermia-induced animals without bupiv acaine) received, under the same experimental conditions, an equivalen t volume of saline. Hyperthermia-induced animals (Groups B and D) were placed in a water-bath at 40 degrees C. Bupivacaine or saline were ad ministered (Group B and D) four hours after the beginning of the exper iment and blood samples were obtained by retro-orbital sinus puncture 0.25, 0.5, 1, 2, 4 and 8 hr after administration. Bupivacaine and its main metabolite, 2,6 desbutylbupivacaine (PPX) were assayed according to a gas liquid chromatographic method. The Cmax, Tmax, t(1/2), Cl, Vd and AUC were determined according to a two compartment open model. Ou r data have demonstrated a decrease in clearance of bupivacaine (5.85 +/- 0.23 ml.hr(-1) and 4.59 +/- 0.35 ml.hr(-1) for groups A and B, res pectively, P < 0.05, and Tmax of PPX during hyperthermia (0.25 +/- 0.0 3 hr and 0.15 +/- 0.0 hr for Groups A and B, respectively, P < 0.05). In conclusion, hyperthermia induces a decrease in bupivacaine clearanc e in rats which may be of importance in clinical practice.