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.