title: Bupivacaine kinetics during hyperthermia in rats.
abstract: 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.
authors.affiliation: Medical Pharmacology Laboratory, Faculty of Medicine of Marseille, France.
authors.forename: B
authors.initials: B
authors.lastname: Bruguerolle
authors.forename: X
authors.initials: X
authors.lastname: Roucoules
authors.forename: L
authors.initials: L
authors.lastname: Attolini
authors.forename: A M
authors.initials: AM
authors.lastname: Lorec
mesh_terms: D000818:Animals; D001831:Body Temperature; D002045:Bupivacaine / Q000031:analogs & derivatives / Q000097:blood / Q000493:pharmacokinetics*; D005334:Fever / Q000097:blood / Q000378:metabolism; D006207:Half-Life; D006979:Hyperthermia, Induced; D008297:Male; D008657:Metabolic Clearance Rate; D051381:Rats; D017208:Rats, Wistar
chemical_list: C025149:2',6'-pipecoloxylidide; D002045:Bupivacaine