Age and gender effects on chlordiazepoxide kinetics: relation to antipyrine disposition.
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 less than 0.001), but was not related to age or sex. Among male subjects, elimination half-life was prolonged (20 vs. 8 h, p less than 0.025) and clearance reduced (20 vs. 43 ml/min, p less than 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 less than 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.
Greenblatt
D J
DJ
Department of Psychiatry, Tufts University School of Medicine, Boston, Mass.
Divoll
M K
MK
Abernethy
D R
DR
Ochs
H R
HR
Harmatz
J S
JS
Shader
R I
RI
D000328:Adult; D000375:Aging / Q000378:metabolism; D000983:Antipyrine / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001835:Body Weight / Q000187:drug effects; D002707:Chlordiazepoxide / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005260:Female; D006207:Half-Life; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D012737:Sex Factors
D002707:Chlordiazepoxide; D000983:Antipyrine