The Influence of Verapamil and Nicardipine on the Rate of Metabolism of Midazolam
UNIFORMED SERVICES UNIV OF THE HEALTH SCIENCES BETHESDA MD BETHESDA United States
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Certified Registered Nurse Anesthetists administer numerous drugs to surgical patientswho may be on a wide and varied pharmacological regimen. It is important that the nurseanesthetist be aware of potential drug-drug interactions. The purpose of this study is toassess the in vitro metabolic reactions of midazolam in the presence of the calciumchannel blockers verapamil and nicardipine in hepatic microsomes from three differenthuman livers. Midazolam a widely used premedicant in anesthesia, and the calciumchannel blockers verapamil and nicardipine are all metabolized by the cytochrome P4503A4 subfamily of liver microsomal enzymes. Recent clinical observations andexperimental studies suggest that midazolam s effects can be augmented by microsomalinhibition when drugs compete for the same family of metabolizing enzymes. In thisstudy the metabolism of midazolam s major metabolite alpha hydroxymidazolam wasmeasured in the presence of differing concentrations of calcium channel blockers usinghuman liver microsomes. Data were analyzed using regression analysis to determine the percent of inhibition and metabolism and Lineweaver-Burk plots were used to determinethe inhibition constant Ki. The mean Ki for nicardipine was 1.35 and 29.3 forverapamil. Nicardipine was the stronger inhibitor of the two calcium channel blockers.Midazolam s effects in the presence of nicardipine and verapamil may be augmented orprolonged.