Age and gender effects on chlordiazepoxide kinetics: Relation to antipyrine disposition

David J. Greenblatt, Marcia K. Divoll, Darrell R. Abernethy, Hermann R. Ochs, Jerold S. Harmatz, Richard I. Shader

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)327-334
Number of pages8
JournalPharmacology
Volume38
Issue number5
DOIs
StatePublished - Jan 1 1989

Keywords

  • Antipyrine
  • Benzodiazepines
  • Chlordiazepoxidc
  • Geriatrics
  • Pharmacokinetics

ASJC Scopus subject areas

  • Pharmacology

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    Greenblatt, D. J., Divoll, M. K., Abernethy, D. R., Ochs, H. R., Harmatz, J. S., & Shader, R. I. (1989). Age and gender effects on chlordiazepoxide kinetics: Relation to antipyrine disposition. Pharmacology, 38(5), 327-334. https://doi.org/10.1159/000138553