FREE NEJM E-TOC    HOME   |   SUBSCRIBE   |   CURRENT ISSUE   |   PAST ISSUES   |   COLLECTIONS   |   Search Term  Advanced Search

Sign in | Get NEJM's E-Mail Table of Contents — Free | Subscribe

Previous Volume 310:1639-1643 June 21, 1984 Number 25 Next

	Add to Personal Archive Add to Citation Manager Notify a Friend E-mail When Cited PubMed Citation

Abstract

Cimetidine is known to impair the hepatic microsomal oxidation of diazepam, reducing its clearance and prolonging its half-life. We studied the clinical importance of this effect in 10 patients, who were receiving long-term treatment with diazepam for anxiety, tension, or difficulty in sleeping, in an eight-week double-blind controlled study during which the diazepam dosage remained constant. The study was in four two-week phases: base-line or adaptation, coadministration of cimetidine (300 mg) or matching placebo four times daily, crossover to the opposite treatment (placebo or cimetidine), and recovery treatment with diazepam alone. During the cimetidine phase, plasma concentrations of diazepam plus desmethyldiazepam rose an average of 57 per cent (P less than 0.005), then fell when cimetidine was withdrawn. However, there were no significant changes in scores on the digit-symbol-substitution test, a tracking task, or a reaction-time test. Clinical self-ratings indicated no increases in sedation, fatigue, or drowsiness. Patients experienced shortening of sleep latency (P less than 0.05) and an increase in self-rated depth or soundness of sleep (P less than 0.001) during the cimetidine period, but there were no changes in sleep duration or in the number of nocturnal awakenings. Although coadministration of cimetidine to diazepam-treated patients causes a large increase in plasma diazepam and desmethyldiazepam concentrations, the increase is of minimal clinical importance.

This article has been cited by other articles:

• Kosuge, K., Jun, Y., Watanabe, H., Kimura, M., Nishimoto, M., Ishizaki, T., Ohashi, K. (2001). Effects of CYP3A4 Inhibition by Diltiazem on Pharmacokinetics and Dynamics of Diazepam in Relation to CYP2C19 Genotype Status. Drug Metab. Dispos. 29: 1284-1289 [Abstract] [Full Text]  
• Abernethy, D. R., Flockhart, D. A. (2000). Molecular Basis of Cardiovascular Drug Metabolism : Implications for Predicting Clinically Important Drug Interactions. Circulation 101: 1749-1753 [Full Text]  
• Grocott, H. P., Grichnik, K. P., Reves, J.G. (1997). Benzodiazepines in Cardiovascular Surgery. SEMIN CARDIOTHORAC VASC ANESTH 1: 109-120  
• Greenblatt, D. J., Harmatz, J. S., Engelhardt, N., Shader, R. I. (1989). Pharmacokinetic Determinants of Dynamic Differences Among Three Benzodiazepine Hypnotics: Flurazepam, Temazepam, and Triazolam. Arch Gen Psychiatry 46: 326-332 [Abstract]