KETAMINE EFFECTS ON BUPIVACAINE LOCAL-ANESTHETIC ACTIVITY AND PHARMACOKINETICS OF BUPIVACAINE IN MICE

This study was designed to document possible changes in bupivacaine (B ) local anaesthetic activity and pharmacokinetics in mice after a keta mine (K) injection. In the experiments, bupivacaine (8.25 mg.kg(-1)), was injected into the popliteal space of the right posterior limb: the local anaesthetic activity was assessed according to a sciatic nerve blockade method with three different doses (2, 10 and 40 mg/kg) of ket amine and the kinetics were studied after a 10 mg/kg dose. When ketami ne was associated, the local anesthetic activity of bupivacaine was si gnificantly enhanced as well as its elimination half-life. Significant ly lower levels of the main metabolite, PPX, were observed, when ketam ine was associated, suggesting a metabolic inhibition phenomenon. The ketamine-induced increase in the total anaesthetic effect of bupivacai ne may thus be explained by kinetic modifications i.e. a possible inhi biting effect of ketamine on the metabolism of bupivacaine.