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Disposition of chlordiazepoxide: Sex differences and effects of oral contraceptives
Author(s) -
Roberts Roderick K.,
Desmond Paul V.,
Wilkinson Grant R.,
Schenker Steven
Publication year - 1979
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1002/cpt1979256826
Subject(s) - chlordiazepoxide , disposition , medicine , research methodology , pharmacology , physiology , population , psychology , environmental health , social psychology , diazepam
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 (t ½ β) 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 1/kg to 0.40 ± 0.14 1/kg) than women not on OC steroids. The elimination t ½ 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.