Effects of Age, Gender and Oral Contraceptives on Intramuscular Midazolam Pharmacokinetics

Abstract

The effects of age, gender and low-dose (50 mcg or less) oral contraceptive steroids (OCS) on the pharmacokinetics of midazolam were evaluated following a single 7.5 mg intramuscular dose to five groups (8/group) of healthy volunteers consisting of young males, young females, elderly males, elderly females, and young female users of oral contraceptives. Blood samples were collected at specified times over a 24-hour period, and plasma concentrations of midazolam and its 1-hydroxymethyl metabolite were determined by a GC-EC assay. Midazolam was rapidly absorbed following intramuscular administration to the different groups. Comparison of young men vs elderly men, young women vs elderly women, young men vs young women, elderly men vs elderly women, and young women OCS-users vs young women non-OCS users indicated no substantial differences in the pharmacokinetic profile of midazolam between groups except for the comparison between the young and elderly men groups. The rate of elimination of midazolam was significantly slower in the elderly males compared to the young men. The pharmacokinetic profile of 1-hydroxymethyl midazolam paralleled that of the parent compound. This is to be expected since this metabolite exhibits formation rate-limited kinetics. Except for one subject who reported hives and itching, considered to be remotely related to test drug, no other adverse experiences or laboratory abnormalities were reported.