SEASONAL-VARIATIONS IN THE KINETICS OF BUPIVACAINE IN THE MOUSE

Very few studies have been devoted to the influence of the time of the year, i.e. seasonal variations, on drug kinetics. This study aims to evaluate whether or not the kinetics of bupivacaine varied according t o the rime of the year in mice. Eight groups of 30 animals each receiv ed bupivacaine (20 mg/kg i.p.) at a specific month of the year, i.e. F ebruary (second week), March (first week), May (fourth week), July (fi rst week), September (fourth week), November (second and third weeks) and December (first week), at the same time of the day (10.00 h). Tota l bupivacaine serum concentrations were determined by using a specific gas liquid chromatographic method on blood samples collected by decap itation at 0.25, 0.5, 1, 2, 3 and 6 h after drug administration. Pharm acokinetic variables were determined, according to a non linear fittin g method (two compartment open model). All data were compared by ANOVA and the influence of the month of the year was estimated by Cosinor a nalysis. According to the month of the year, the kinetic parameters we re significantly different except for V-d: the maximal C-max occurred in July, the highest T-max occurred in May, the maximal T(1/2)beta and the maximal AUC were observed in February. The mechanisms underlying these variations may depend on seasonal variations of resorption, dist ribution, metabolism and elimination.