Zopiclone Rifampicin

Rifampicin, and presumably other enzyme inducers, reduces concentrations of zolpidem, zopiclone, and buspirone (SEDA-22, 42). Drugs that are solely glucuroni-dated (lorazepam, oxazepam, and temazepam) are not affected. 

ZALEPLON, ZOLPIDEM, ZOPICLONE ANTIBIOTICS-RIFAMPICIN -l levels of these hypnotics Induction of CYP3A4-mediated metabolism Watch for poor response to these agents... 

Zaleplon, zolpidem and zopiclone are metabolised by several cytochrome CYP450 isoenzymes and it has been suggested that because of this, other drugs which affect a particular isoenzyme such as CYP3A4, may have less effect on their metabolism. However, their pharmacokinetics are affected by potent inducers such as rifampicin and by inhibitors such as the azole antifungals. Buspirone undergoes CYP3A4-mediated metabolism in the liver. 

In a two-phase study, 8 healthy subjects were given rifampicin 600 mg or a placebo daily for 5 days, with a single 10-mg oral dose of zopiclone on day 6. The rifampicin r uced the zopiclone AUC by 82%, decreased the peak serum levels by 71% and reduced its half-life from 3.8 to 2.3 hours. A significant reduction in the effects of zopiclone was also seen, as measured by the performance of psychomotor tests. ... 

Rifampicin is a potent liver enzyme inducer, which increases the metabolism of several benzodiazepines and the non-benzodiazepine hypnotics, zaiepion, zoipidem and zopiclone, thereby decreasing their levels. The metabolism of midazolam by the cytochrome P450 isoenzyme CYP3A4 in both liver and gut is affected. The enzyme inducing effects of rifampicin seem to predominate if isoniazid (an enzyme inhibitor) is also present. Temazepam undergoes glucuronidation and is therefore unaffected by rifampicin. 

The effect of rifampicin on oral midazolam, triazolam, zaiepion, zoipidem and zopiclone is so large that they are likely to become ineffective and an alternative should be used instead. Alprazolam is also predicted to interact because CYP3A is involved with its metabolism. ... 

Villikka K, Kivistb KT, Lam berg TS, Kantola T, Neuvonen PJ. Concentrations and effects of zopiclone are greatiy reduced by rifampicin. BrJ Clin Pharmacol (1997) 43,471-4. 

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See also in sourсe #XX -- [ ]

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