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Population study of triazolam pharmacokinetics
British Journal of Clinical Pharmacology
|December 1, 1986
Summary
The pharmacokinetics of triazolam show wide variability in healthy young men, with elimination half-life averaging 2.6 hours. Peak plasma levels strongly correlate with clearance and AUC, not body weight.
Area of Science:
- Pharmacology
- Pharmacokinetics
- Drug Metabolism
Background:
- Triazolam is a triazolobenzodiazepine hypnotic.
- Understanding its pharmacokinetic profile is crucial for safe and effective use.
Purpose of the Study:
- To investigate the pharmacokinetics of a single oral dose of triazolam.
- To determine key kinetic variables and their distribution in healthy young men.
Main Methods:
- A single 0.5 mg oral dose of triazolam was administered to 54 healthy young men.
- Plasma concentrations were measured over 14 hours post-dose.
- Kinetic variables were analyzed for distribution using the Kolmogorov-Smirnov Goodness of Fit test.
Main Results:
- Mean elimination half-life was 2.6 hours. Peak plasma concentration (4.4 ng/mL) and total AUC (19.1 ng·mL/h) showed wide ranges.
- Kinetic variables followed Poisson and log-normal distributions, not normal distributions.
- Peak plasma levels strongly correlated with clearance (r=-0.85) and AUC (r=0.85), but not body weight.
Conclusions:
- Triazolam pharmacokinetics exhibit significant inter-individual variability even in a homogeneous group.
- Body weight is not a reliable predictor of triazolam clearance or peak plasma levels.
- The non-normal distribution of kinetic variables suggests complex metabolic pathways or absorption.