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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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