A study of the in vitro interaction between lidocaine and premedications using human liver microsomes.
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 microM). Thiamylal was a competitive inhibitor of lidocaine metabolism (Ki = 885 microM). 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.


CONCLUSIONS
These results show that the interactions between lidocaine and midazolam and thiamylal are of potential toxicological and clinical significance.
Nagashima
A
A
Institute of Community Medicine, University of Tsukuba, Ibaraki-ken, Japan.
Tanaka
E
E
Inomata
S
S
Honda
K
K
Misawa
S
S
D000818:Animals; D002927:Cimetidine / Q000378:metabolism / Q000493:pharmacokinetics; D003000:Clonidine / Q000493:pharmacokinetics; D019388:Cytochrome P-450 CYP1A2 / Q000378:metabolism; D065609:Cytochrome P-450 CYP1A2 Inhibitors; D051544:Cytochrome P-450 CYP3A; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D020128:Inhibitory Concentration 50; D007654:Ketoconazole / Q000378:metabolism / Q000493:pharmacokinetics; D008012:Lidocaine / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000493:pharmacokinetics*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008874:Midazolam / Q000378:metabolism / Q000493:pharmacokinetics; D009467:Neuromuscular Depolarizing Agents / Q000737:chemistry / Q000378:metabolism / Q000493:pharmacokinetics; D010424:Pentobarbital / Q000378:metabolism / Q000493:pharmacokinetics; D010597:Pharmacogenetics / Q000379:methods; D011292:Premedication; D051381:Rats; D013806:Theophylline / Q000031:analogs & derivatives / Q000378:metabolism / Q000493:pharmacokinetics; D013840:Thiamylal / Q000378:metabolism / Q000493:pharmacokinetics
D065609:Cytochrome P-450 CYP1A2 Inhibitors; D065607:Cytochrome P-450 Enzyme Inhibitors; D004338:Drug Combinations; D004791:Enzyme Inhibitors; D009467:Neuromuscular Depolarizing Agents; D013840:Thiamylal; D002927:Cimetidine; D003577:Cytochrome P-450 Enzyme System; D008012:Lidocaine; D013806:Theophylline; C050131:furafylline; C001173:monoethylglycinexylidide; C104464:CYP3A protein, human; D019388:Cytochrome P-450 CYP1A2; D051544:Cytochrome P-450 CYP3A; D010424:Pentobarbital; D003000:Clonidine; D008874:Midazolam; D007654:Ketoconazole