A study of the in vitro interaction between lidocaine and premedications using human liver microsomes*


  • *

    Part of this study was presented at the 14th International Symposium on Microsomes and Drug Oxidations, 22–26 July, 2002, Sapporo, Japan.

Dr Einosuke Tanaka, Institute of Community Medicine, University of Tsukuba, Tsukuba-shi, Ibaraki-ken 305-8575, Japan. Tel./Fax: +81 29 853 3057; e-mail: einosuke@md.tsukuba.ac.jp


Objective:  To investigate potential interactions between lidocaine (lignocaine) metabolism and premedication drugs, i.e. psychotropic and antianxiety agents (diazepam, midazolam), hypnotics (pentobarbital, thiamylal), depolarizing neuromuscular blocking agents (vecuronium, pancuronium and suxamethonium), an antihypertensive agent (clonidine) and an H2-receptor blocking agent (cimetidine) using human liver microsomes in vitro.

Methods:  The interaction effects between lidocaine and premedication were examined using human liver microsomal preparations and monitored for enzyme activity. The lidocaine and its main metabolite (monoethylglycinexylide) were measured by HPLC/UV.

Results:  Lidocaine metabolism was non-competitively inhibited by midazolam (Ki = 77·6 μm). Thiamylal was a competitive inhibitor of lidocaine metabolism (Ki = 885 μm). Cimethidine, pancuronium and vecuronium weakly inhibited lidocaine metabolism in a concentration-depend manner over the therapeutic range in human liver microsomes. On the contrary, suxamethonium, pentobarbital and clonidine did not inhibit lidocaine metabolism over the therapeutic range in human liver microsomes.

Conclusion:  These results show that the interactions between lidocaine and midazolam and thiamylal are of potential toxicological and clinical significance.