Differential effects of oral contraceptive steroids on the metabolism of benzodiazepines

The effects of oral contraceptive steroids (OCS) on the disposition and elimination of lorazepam, oxazepam, and chlordiazepoxide were examined. Lorazepam and oxazepam are metabolized via glucuronidation while chlordiazepoxide is metabolized by oxidation in the liver. The disposition and elimination of lorazepam, oxazepam, and chlordiazepoxide was studied in females not taking OCS and females taking OCS (norethindrone acetate, 1 mg; ethinyl estradiol, 50 μg) for 6 months or more. The t 1/2 (β) for lorazepam was significantly reduced in women taking OCS (6.0 ± 3.1 vs. 14.0 ± 6.2 hr) (p <0.005) as compared to controls, and the t 1/2 (β) for oxazepam was reduced in women taking OCS (7.71 ± 3.23 vs. 12.09 ± 5.08 hr) as compared to controls, but did not reach statistical significance. The plasma clearance of both lorazepam and oxazepam was significantly increased in women taking OCS [(288.9 ± 165.9 vs. 77.5 ± 3.29 ml per min) (p