Abstract
Twelve normal subjects aged 24-41 years, and 12 subjects aged 62-79 years, received single 50-mg doses of chlordiazepoxide hydrochloride by mouth and by intravenous injection on two occasions. Chlordiazepoxide volume of distribution was significantly correlated with body weight (r = 0.63, p < 0.001), but was not related to age or sex. Among male subjects, elimination half-life was prolonged (20 vs. 8 h, p < 0.025) and clearance reduced (20 vs. 43 ml/min, p < 0.05) in elderly as opposed to young volunteers. Among women, there was no significant difference between elderly and young subjects in elimination half-life (12 vs. 13 h) or clearance (29 vs. 22 ml/min). Absolute bioavailability of oral chlordiazepoxide was not less than 100%, and was unrelated to age or sex. Among 20 subjects who received a single 1.0- to 1.2-gram intravenous dose of antipyrine on another occasion, clearance of chlordiazepoxide and of antipyrine were significantly correlated (r = 0.62, p < 0.01). Like many other low-clearance oxidatively metabolized compounds, chlordiazepoxide clearance is reduced and half-life prolonged in elderly men, but not elderly women. Individual variations in chlordiazepoxide clearance are significantly correlated with those of antipyrine, a drug commonly used as an index of hepatic oxidizing capacity.
Original language | English (US) |
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Pages (from-to) | 327-334 |
Number of pages | 8 |
Journal | Pharmacology |
Volume | 38 |
Issue number | 5 |
DOIs | |
State | Published - 1989 |
Externally published | Yes |
Keywords
- Antipyrine
- Benzodiazepines
- Chlordiazepoxidc
- Geriatrics
- Pharmacokinetics
ASJC Scopus subject areas
- Pharmacology