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  • Title: Differential effects of oral contraceptive steroids on the metabolism of benzodiazepines.
    Author: Patwardhan RV, Mitchell MC, Johnson RF, Schenker S.
    Journal: Hepatology; 1983; 3(2):248-53. PubMed ID: 6131860.
    Abstract:
    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 micrograms) for 6 months or more. The t1/2 (beta) for lorazepam was significantly reduced in women taking OCS (6.0 +/- 3.1 vs. 14.0 +/- 6.2 hr) (p less than 0.005) as compared to controls, and the t1/2 (beta) 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 less than 0.01) and (251.2 +/- 106.9 vs. 97.86 +/- 69.4 ml per min) (p less than 0.01), respectively] as compared to controls. The volumes of distribution of lorazepam and oxazepam were significantly increased in women taking OCS (p less than 0.05) while plasma binding of these drugs was similar in both groups. In contrast, the t1/2 (beta) of chlordiazepoxide was significantly prolonged (20.58 +/- 8.08 vs. 11.63 +/- 5.91 hr) (p less than 0.05), and the plasma clearance was significantly reduced (13.41 +/- 4.69 vs. 33.22 +/- 12.37 ml per min) (p less than 0.05) in the OCS group as compared to controls. The volumes of distribution of chlordiazepoxide were similar in both groups, and the plasma binding of chlordiazepoxide tended to be lower in the OCS group but did not reach statistical significance. We conclude that OCS exert a differential effect on the elimination of benzodiazepines, whereby oxidation of chlordiazepoxide is impaired while the glucuronidation of lorazepam and oxazepam is enhanced by OCS.
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