alexa Comparison of the effects of intravenously administered midazolam, triazolam and their hydroxy metabolites.
Pharmaceutical Sciences

Pharmaceutical Sciences

Journal of Bioequivalence & Bioavailability

Author(s): Ziegler WH, Schalch E, Leishman B, Eckert M

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Abstract The aim of the study was to compare the pharmacological activity and clinical effect after i.v. administration of midazolam, triazolam and their hydroxy metabolites, and, secondly, to compare the clinical effects of midazolam and triazolam in doses yielding the same duration of action (15 mg and 0.25 mg, respectively). In a randomized, cross-over procedure, six healthy volunteers received one of the following in the morning at approximately weekly intervals: 15 mg midazolam; 9 mg alpha-hydroxy midazolam; 1 mg triazolam; 1 mg alpha-hydroxy triazolam; 1 mg 4-hydroxy triazolam. Tests of drug effect (investigator's assessment, psychometric testing, and self-rating by subjects) were carried out at different times in the 24-h period following administration. Triazolam 0.25 mg was also studied in four of these six subjects to supplement the findings in the cross-over study. Triazolam 1 mg was shown to have the strongest, most long-lasting effect. Midazolam 15 mg had almost the same intensity of effect but this was shorter lasting, i.e. 5 h as against 10 h for 1 mg triazolam. The alpha-hydroxy metabolites had a duration of action about half that of the parent compounds and a less potent effect, and 4-hydroxy triazolam was virtually devoid of effect. The lower 0.25-mg dose of triazolam had about the same duration of action as 15 mg midazolam but did not achieve the same degree of maximum effect as measured by psychometric tests and self-assessment by subjects. The findings of this study indicate that midazolam would be suitable for use in situations in which a brief but intense hypnotic sedative effect is desired.
This article was published in Br J Clin Pharmacol and referenced in Journal of Bioequivalence & Bioavailability

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