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  • Title: Disposition of chlordiazepoxide: sex differences and effects of oral contraceptives.
    Author: Roberts RK, Desmond PV, Wilkinson GR, Schenker S.
    Journal: Clin Pharmacol Ther; 1979 Jun; 25(6):826-31. PubMed ID: 445949.
    Abstract:
    There is considerable interspecies and interdrug variability in the effect of sex differences and oral contraceptive (OC) steroids on hepatic drug elimination. Their influence on the disposition of chlordiazepoxide has been studied in 11 healthy young men (29 +/- 5 yr), 11 healthy young women (28 +/- 5 yr), and 7 healthy women receiving OC steroids (27 +/- 2 yr) for more than 6 months. The elimination half-life (t1/2(beta)) was longer (from 14.8 +/- 5.9 hr to 8.9 +/- 2.5 hr) and protein binding less (95.5 +/- 1.4% and 97.0 +/- 1.2%) in women than in men. Weight-normalized plasma clearances of total drug did not differ, but the clearance of unbound drug was significantly less in women (8.7 +/- 5.0 ml/min/kg) than in men (15.6 +/- 5.3 ml/min/kg). Women on OC steroids had a lower plasma binding (from 93.6 +/- 1.5% to 95.5 +/- 1.4%) and a higher volume of distribution (from 0.62 +-/ 0.23 l/kg to 0.40 +/- 0.14 l/kg) than women not on OC steroids. The elimination t1/2 was longer (from 24.3 +/- 12 hr to 14.8 +/- 5.9 hr) and the clearance of unbound drug lower (from 5.7 +/- 3.0 ml/min/kg to 8.7 +/- 5.0 ml/min/kg) in women on OC steroids than in those not using them, but these differences were not statistically significant. The effect of oral contraceptives (OCs) on hepatic drug elimination, in this case chlordiazepoxide, was studied in 11 healthy young men, 11 healthy young women, and 7 healthy young women receiving OCs for more than 6 months. Elimination half-life was longer (14.8-8.9 hours) and the protein binding less (95.5 and 97%) in women than in men. When weights were normalized, plasma clearances of total drug did not differ, but clearance of unbound drug was significantly less in women (8.7 ml/min/kg) than in men (15.6 ml/min/kg). Women taking OCs had a lower plasma binding (from 93.6-95.5%) and a higher volume of distribution (from .62-4 1/kg) than women not taking OCs. Elimination half-life was longer (from 23.4-14.8 hours) and clearance of unbound drug lower (from 5.7-8.7 ml/min/kg) in women on OCs than in those not using them, but these differences were not statistically significant.
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