A large-sample study of diazepam pharmacokinetics.
Healthy male volunteers (n = 48) aged 18-44 years received a single 10-mg oral dose of diazepam. Plasma diazepam and desmethyldiazepam concentrations were measured at multiple points during the next 11 days. The distribution of peak plasma concentration (mean, 406 ng/ml) was not skewed and did not differ significantly from normal (Guassian). However, the distributions of elimination half-life (44.2 h), elimination rate constant (0.0219/h), clearance (26.6 ml/min), and volume of distribution (83 L) all were significantly skewed and deviated significantly fron normal. After logarithmic transformation, the distributions of elimination rate constant, elimination half-life, and volume of distribution were consistent with normal; however, this was not the case for time of peak plasma concentration. Thus, the pharmacokinetic characteristics of oral diazepam are highly variable even in a relatively homogeneous population. Parametric statistical testing procedures and pharmacokinetic forecasting schemes may be improved by more precise delineation of the underlying distributions for pharmacokinetic variables.
Greenblatt
D J
DJ
Department of Psychiatry, Tufts University School of Medicine, Boston, Massachusetts.
Harmatz
J S
JS
Friedman
H
H
Locniskar
A
A
Shader
R I
RI
D000293:Adolescent; D000328:Adult; D001835:Body Weight; D002849:Chromatography, Gas; D003975:Diazepam / Q000493:pharmacokinetics*; D006207:Half-Life; D006801:Humans; D008297:Male; D003708:Nordazepam / Q000097:blood
D003708:Nordazepam; D003975:Diazepam