TRIAZOLAM IS INEFFECTIVE IN PATIENTS TAKING RIFAMPIN

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 dr ugs such as midazolam, The possible interaction between rifampin and t riazolam was examined in this study, Methods:The pharmacokinetics and pharmacodynamics of triazolam were investigated in a randomized, doubl e-blind crossover study with two phases. Ten young healthy volunteers took either 600 mg rifampin once daily or placebo for 5 days. On the s ixth day, 0.5 mg triazolam was administered orally, Timed blood sample s were collected and the effects of triazolam were measured with five psychomotor tests for 10 hours. Results: The area under the plasma tri azolam 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 max imum 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 elim ination half-life from 2.8 +/- 0.1 to 1.3 +/- 0.1 hours (p < 0.001). A ll psychomotor tests showed markedly reduced effects (p < 0.01) of tri azolam after rifampin pretreatment. Conclusions: Triazolam is ineffect ive during rifampin treatment. This is most likely due to increased me tabolism of triazolam after induction of CYP3A4 in the gut wall and li ver by rifampin. It is advisable to use hypnotic agents that are not m etabolized by CYP3A4 during treatment with rifampin or other potent in ducers of CYP3A4.