A Large‐Sample Study of Diazepam Pharmacokinetics
作者:
David Greenblatt,
Jerold Harmatz,
H. Friedman,
Ann Locniskar,
Richard Shader,
期刊:
Therapeutic Drug Monitoring
(OVID Available online 1989)
卷期:
Volume 11,
issue 6
页码: 652-657
ISSN:0163-4356
年代: 1989
出版商: OVID
关键词: Diazepam;Desmethyldiazepam;Populations;Pharmacokinetics.
数据来源: OVID
摘要:
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 (Gaussian). 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 from 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.
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