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Triazolam is ineffective in patients taking rifampin
Author(s) -
Villikka Kirsti,
Kivistö Kari T.,
Backman Janne T.,
Olkkola Klaus T.,
Neuvonen Pertti J.
Publication year - 1997
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1016/s0009-9236(97)90176-4
Subject(s) - triazolam , midazolam , hypnotic , pharmacology , pharmacokinetics , placebo , cyp3a4 , crossover study , pharmacodynamics , anesthesia , chemistry , medicine , benzodiazepine , sedation , cytochrome p450 , metabolism , receptor , alternative medicine , pathology
Background Triazolam is metabolized predominantly by cytochrome P450 3A4 (CYP3A4). Rifampin (rifampicin) is a potent inducer of CYP3A4 and it is known to markedly reduce plasma concentrations and effects of drugs such as midazolam. The possible interaction between rifampin and triazolam was examined in this study. Methods The pharmacokinetics and pharmacodynamics of triazolam were investigated in a randomized, double‐blind crossover study with two phases. Ten young healthy volunteers took either 600 mg rifampin once daily or placebo for 5 days. On the sixth day, 0.5 mg triazolam was administrered orally. Timed blood samples were collected and the effects of triazolam were measured with five psychomotor tests for 10 hours. Results The area under the plasma triazolam concentration‐time curve in the rifampin phase was only 5.1% of that in the placebo phase (0.74 ± 0.14 versus 14.8 ± 1.0 ng · hr/ml [mean ± SEM; p < 0.001]). Rifampin pretreatment decreased the maximum plasma concentration of triazolam to 12.4% of the control value (i.e., from 2.9 ± 0.2 to 0.36 ± 0.06 ng/ml [ p < 0.001]) and the elimination half‐life from 2.8 ± 0.1 to 1.3 ± 0.1 hours ( p < 0.001). All psychomotor tests showed markedly reduced effects ( p < 0.01) of triazolam after rifampin pretreatment. Conclusions Triazolam is ineffective during rifampin treatment. This is most likely due to increased metabolism of triazolam after induction of CYP3A4 in the gut wall and liver by rifampin. It is advisable to use hypnotic agents that are not metabolized by CYP3A4 during treatment with rifampin or other potent inducers of CYP3A4. Clinical Pharmacology & Therapeutics (1997) 61 , 8–14; doi: