Effect of Gender on the Rate of Metabolism of Midazolam in Humans Using Liver Microsomes.

摘要

Midazolam (MDZ) is a short-acting benzodiazepine used in anesthesia for its anxiolytic, sedative, and amnestic properties. MDZ has a variable and unpredictable effect among individuals, which has the potential to complicate patient care and prolong hospital stay. It has been reported that inter-individual differences in the rate of metabolism are the primary cause of variances in the drug's therapeutic effect. MDZ is metabolized almost exclusively by the cytochrome P-450 3A subfamily (CYP3A). The drug is eliminated to a major metabolite, 1'-hydroxymidazolam, which accounts for at least 70% of an administered dose. MDZ forms a minor metabolite, 4-hydroxymidazolam, which comprises about 4% of an administered dose, and is also metabolized by CYP3A. The objective of this study is to determine, using human liver microsomes, if there is a gender difference in the rate of MDZ metabolism to both 1' and 4-hydroxymidazolam.