Bupivacaine kinetics during hyperthermia in rats

The aim of this study was to document possible alterations of bupivacaine pharmacokinetic behaviour in rats during hyperthermia. Two groups of Wistar AF IO PS 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 without bupivacaine, Group D = hyperthermia-induced animals without bupivacaine) received, under the same experimental conditions, an equivalent volume of saline. Hyperthermia-induced animals (Groups B and D) were placed in a water-bath at 40 degrees C. Bupivacaine or saline were administered (Group B and D) four hours after the beginning of the experiment 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, t1/2, Cl, Vd and AUC were determined according to a two compartment open model. Our 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, respectively, P < 0.05, and, Tmax of PPX during hyperthermia (0.24 +/- 0.03 hr and 0.15 +/- 0.0 hr for Groups A and B, respectively, P < 0.05). In conclusion, hyperthermia induces a decrease in bupivacaine clearance in rats which may be of importance in clinical practice.