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Pharmacokinetic Determinants of Dynamic Differences Among Three Benzodiazepine HypnoticsFlurazepam, Temazepam, and Triazolam
David J. Greenblatt, MD;
Jerold S. Harmatz;
Nina Engelhardt;
Richard I. Shader, MD
Arch Gen Psychiatry. 1989;46(4):326-332.
Abstract
• Healthy adult volunteers (n = 52) received single oral doses of flurazepam hydrochloride (15 mg), temazepam (15 mg), triazolam (0.25 mg), or placebo in a parallel, double-blind study. Sedative effects were greatest with triazolam, followed next by temazepam; peak effects closely coincided with peak plasma concentrations. Differential recovery from sedation corresponded in part to differences in mean elimination halflife, although sedative effects returned to baseline before plasma drug concentrations became undetectable. Sedation following flurazepam administration was less intense than with triazolam and temazepam. When tested at three hours after dosing, none of the active treatments impaired learning of a 16-item word list. However, at 24 hours, triazolam recipients could not recall a significant fraction of what was learned. Thus, dynamic differences among three benzodiazepine hypnotics may be partly explained by kinetic differences, as well as, we should caution, by possible "clinical inequivalence" in dosage.
Author Affiliations
From the Division of Clinical Pharmacology, Departments of Psychiatry and Medicine, Tufts University School of Medicine and New England Medical Center, Boston.
Footnotes
Accepted for publication April 1, 1988.
Presented in part at the 89th Annual Meeting of the American Society for Clinical Pharmacology and Therapeutics, San Diego, March 10, 1988.
Reprint requests to Division of Clinical Pharmacology, Tufts—New England Medical Center, Box 1007, 171 Harrison Ave, Boston, MA 02111 (Dr Greenblatt).
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