KINETICS OF BUPIVACAINE AFTER LEVCROMAKALIM TREATMENT IN MICE

Previous workers have reported that 0.01 mg kg(-1) of levcromakalim in jected intraperitoneally did not modify bupivacaine-induced neurotoxic ity but increased the duration of action of bupivacaine. This study wa s designed to document possible changes in the pharmacokinetic behavio ur of bupivacaine and its main metabolite, N-desbutylbupivacaine in mi ce after a single 0.01 mg kg(-1) intraperitoneal injection of levcroma kalim. The kinetic parameters of bupivacaine were determined after a s ingle 20 mg kg(-1) intraperitoneal injection of bupivacaine in control s and in levcromakalim-treated mice. It was found that levcromakalim d id not change any kinetic parameters of bupivacaine or of its main met abolite N-desbutylbupivacaine. The previously reported findings of the influence of the low dose (0.01 mg kg(-1)) of levcromakalim on bupiva caine-induced toxicity agree well with the lack of influence of 0.01 m g kg(-1) of levcromakalim on bupivacaine and N-desbutylbupivacaine pha rmacokinetics, although the reported increase in the duration of actio n of bupivacaine after levcromakalim treatment can hardly be explained by the pharmacokinetics of bupivacaine when associated with levcromak alim. We suggest that levcromakalim might interfere directly with ion- channel block caused by bupivacaine by altering conduction properties or indirectly by enhancing bupivacaine-induced voltage and time-depend ent sodium-channel block.