Cigarette smoke increases bupivacaine metabolism in rats

This study was designed to document possible changes in bupivacaine kinetics in rats after exposure to cigarette smoke. Rats (n = 15) were exposed to cigarette smoke (Borgwaldt type Hamburg II) for ten minutes per day during four days (C) or eight days (B); controls (A) were used simultaneously without exposure to cigarette smoke. After bupivacaine 20 mg.kg-1 ip at day 4 (C) or day 8 (B), blood was sampled (0.5 ml of blood collected by puncture at the retro-orbital sinus 0.25, 0.5, 1, 2, 4, 6 and 8 hours after administration) and bupivacaine and its main metabolite i.e., desbutylbupivacaine (PPX) were determined by gas liquid chromatography. The sensitivity of the method was 15 ng.ml-1 and the reproductibility was < 6%. Serum bupivacaine concentrations were plotted against time and the pharmacokinetic variables were determined assuming a two compartment open model: Cmax, Tmax were derived directly from individual data. The beta phase elimination half-lives (T1/2 beta), the area under the serum concentration curve (AUC0 infinity), the total plasma clearance (Cl) and the total volume of distribution (Vd) were calculated. These variables were assessed according to non-linear fitting method. Cigarette smoking exposure did not change the pharmacokinetic variables of bupivacaine.(ABSTRACT TRUNCATED AT 250 WORDS)