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A study of the in vitro clinical interaction between lidocaine and premedications using rat liver microsomes

Institute of Community Medicine, University of Tsukuba, Ibaraki-ken 305-8575, Japan

E Tanaka

Institute of Community Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki-ken 3058575, Japan; einosuke{at}md.tsukuba.ac.jp

S Inomata

Institute of Clinical Medicine, University of Tsukuba, Ibaraki-ken 305-8575, Japan

S Misawa

Institute of Community Medicine, University of Tsukuba, Ibaraki-ken 305-8575, Japan

In this study, we have investigated the relationship between lidocaine metabolism and premedication, i.e., psychotropic and anti-anxiety agents (diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing muscular relaxants (vecuronium, pancuronium and suxamethonium), an active anti-hypertensive (clonidine) and an H₂ receptor antagonist (cimetidine) using rat hepatic microsomes in vitro. Lidocaine metabolism was noncompetitively inhibited by midazolam (K_i=29.0 mM). Thilamylal was a moderate competitive inhibitor of lidocaine metabolism (K_i=77.8 mM). Pentobarbital, diazepam and cimetidine weakly inhibited lidocaine metabolism formation in a concentration-dependent manner at high substrate concentrations. On the other hand, vecuronium, pancuronium, suxamethonium and clonidine did not inhibit lidocaine metabolism over the therapeutic range. These results show that the interaction between lidocaine and midazolam and thiamylal, catalyzed by a similar cytochrome P450, is of potential importance in toxicological and clinical studies.

Key Words: cytochrome P450 • drug interaction • hepatic enzyme activity • in vitro metabolism • lidocaine • rat microsomes

Human & Experimental Toxicology, Vol. 21, No. 8, 453-456 (2002)
DOI: 10.1191/0960327102ht279oa


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