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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Rifampin reduces plasma concentrations and effects of zolpidem.

BACKGROUND: Zolpidem is a short-acting imidazopyridine hypnotic drug that is metabolized mainly by CYP3A4. Rifampin (INN, rifampicin) is a potent inducer of many cytochrome P450 enzymes, and it greatly reduces the plasma concentrations and effects of, for example, midazolam, triazolam, and zopiclone. In this study, the effects of rifampin on the pharmacokinetics and pharmacodynamics of zolpidem were studied. METHODS: In a randomized crossover study with two phases and a washout of 4 weeks, eight young healthy female volunteers took either 600 mg rifampin or placebo once a day for 5 days. On day 6, 20 mg zolpidem was administered orally. Plasma concentrations and effects of zolpidem were measured up to 10 hours. RESULTS: The total area under the plasma zolpidem concentration-time curve after administration of rifampin was 27% of that after administration of placebo (336 +/- 67 versus 1202 +/- 157 [mean value +/- SEM; p < 0.01]). Rifampin decreased the peak plasma concentration of zolpidem by 58%, that is, from 293 +/- 61 to 117 +/- 25 ng/ml (p < 0.01) and the elimination half-life from 2.5 +/- 0.2 to 1.6 +/- 0.1 hours (p < 0.01). A significant (p < 0.05) reduction in the effects of zolpidem was seen in all six pharmacodynamic tests after rifampin pretreatment. CONCLUSIONS: The effects of zolpidem are considerably reduced by rifampin because of enhanced metabolism of zolpidem. It is likely that zolpidem also shows a reduced hypnotic effect when used concomitantly with other potent inducers of CYP3A4, such as phenytoin and carbamazepine.[1]


  1. Rifampin reduces plasma concentrations and effects of zolpidem. Villikka, K., Kivistö, K.T., Luurila, H., Neuvonen, P.J. Clin. Pharmacol. Ther. (1997) [Pubmed]
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