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  • Title: Pharmacokinetic consequences of long term coadministration of cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects.
    Author: Pourbaix S, Desager JP, Hulhoven R, Smith RB, Harvengt C.
    Journal: Int J Clin Pharmacol Ther Toxicol; 1985 Aug; 23(8):447-51. PubMed ID: 2864320.
    Abstract:
    The influence of administration of cimetidine (1 g daily for 2 weeks) on the pharmacokinetics of alprazolam (0.5 mg t.i.d. for 1 week) and triazolam (0.5 mg nightly for 1 week) was investigated in two groups of 8 healthy subjects. The plasma AUC of these triazolobenzodiazepines were significantly increased. Moreover, for triazolam, the C max was increased and the plasma elimination half-life was prolonged; oral clearance of the two triazolobenzodiazepines was markedly reduced. It is suggested that the combined treatment cimetidine-alprazolam requires a reduced daily dosage (one third) of alprazolam or increased dosage intervals (b.i.d. instead of t.i.d.). For triazolam, used as a hypnotic drug, such dosage reduction appears unsuitable if administered on a once-nightly basis.
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