KINETICS OF BUPIVACAINE AFTER CLONIDINE PRETREATMENT IN MICE

previous studies have reported that clonidine pretreatment causes an i ncrease in the local anaesthetic activity of bupivacaine. This study w as designed to document possible changes in the pharmacokinetic behavi our of bupivacaine and its main metabolite, desbutylbupivacaine, PPX, in mice after a single, 0.1 mg . kg(-1) injection of clonidine. Kineti c variables of bupivacaine were determined after a single 20 mg . kg(- 1) ip dose of bupivacaine in controls (Group I) and in clonidine (0.1 mg . kg(-1) ip) pretreated mice (Group 2). The maximal concentration i n serum (Cmax, 2.553 +/- 0.862 mu g . ml(-1) versus 0.962 +/- 0.141 mu g . ml(-1) for Groups 2 and I, respectively, P = 0.01) and the area u nder the concentration curve (AUG, 3.530 +/- 0.330 mu g . ml(-1). hr(- 1) versus 1.755 +/- 0.252 mu g . ml(-1). hr(-1) for Groups 2 and I, re spectively, P < 0.01) of bupivacaine were higher in clonidine pretreat ed mice while the Clearance (CI) was decreased in clonidine pretreated animals (0.603 +/- 0.054 mu g . ml(-1) versus 1.264 +/- 0.447 mu g . ml(-1) for Groups 2 and 2, respectively P < 0.01). The ratio of AUC PP X/AUC bupivacaine (which may partially indicate the rate of metabolism ) was lower in presence of clonidine (0.220 +/- 0.019 against 0.425 +/ - 0.033 for Groups 2 and I, respectively P < 0.01). Our data indicate decreased metabolism in the clonidine-treated mice which suggests alte red hepatic metabolism of bupivacaine by clonidine. This may explain t he previously reported enhanced anaesthetic activity of bupivacaine in the presence of clonidine.