Population study of triazolam pharmacokinetics.

Abstract

The kinetics of a single 0.5 mg oral dose of the triazolobenzodiazepine hypnotic triazolam, were studied in 54 healthy young men aged 20‐44 years, with a mean body weight of 77 kg. Triazolam kinetics were determined from multiple plasma concentrations measured during 14 h post‐dose. The overall mean +/‐ s.e. mean (with range) kinetic variables were: peak plasma concentration, 4.4 +/‐ 0.3 (1.7‐9.4) ng ml‐ 1; time of peak, 1.3 +/‐ 0.1 (0.5‐4.0) h after dose; elimination half‐ life, 2.6 +/‐ 0.1 (1.1‐4.4) h; total AUC: 19.1 +/‐ 1.1 (4.4‐47.7) ng ml‐ 1 h; oral clearance, 526 +/‐ 38 (175‐1892) ml min‐1. All kinetic variables were consistent with Poisson distributions, based on the Kolmogorov‐Smirnov Goodness of Fit test. None of the variables fit normal distributions. Four of five were consistent with a log normal distribution. Peak plasma level was highly correlated with clearance (r = −0.85, P less than 0.0001), and AUC (r = 0.85, P less than 0.0001) but not with body weight (r = 0.21, NS). Clearance and body weight were not correlated (r = −0.01). Triazolam clearance may vary widely even within a homogeneous group of healthy young men. 1986 The British Pharmacological Society