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 to the time of the year in mice. Eight groups of 30 animals each received bupivacaine (20 mg/kg i.p.) at a specific month of the year, i.e. February (second week), March (first week), May (fourth week), July (first week), September (fourth week), November (second and third weeks) and December (first week), at the same time of the day (10.00 h). Total bupivacaine serum concentrations were determined by using a specific gas liquid chromatographic method on blood samples collected by decapitation at 0.25, 0.5, 1, 2, 4 and 6 h after drug administration. Pharmacokinetic variables were determined, according to a non linear fitting method (two compartment open model). All data were compared by ANOVA and the influence of the month of the year was estimated by Cosinor analysis. According to the month of the year, the kinetic parameters were 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)β and the maximal AUC were observed in February. The mechanisms underlying these variations may depend on seasonal variations of resorption, distribution, metabolism and elimination.