Mareile H Breithaupt, Evelyn Krohmer, Lenka Taylor, Eva Körner, Torsten Hoppe-Tichy, Juergen Burhenne, Kathrin I Foerster, Markus Dachtler, Gerald Huber, Rakesh Venkatesh, Karin Eggenreich, David Czock, Gerd Mikus, Antje Blank, Walter E Haefeli
BACKGROUND AND PURPOSE: In patients of all ages, metamizole is a frequently used analgesic. Recently, metamizole has been identified as an inducer of, among others, cytochrome P450 (CYP) 3A activity, but the time course of this interaction has not been evaluated. EXPERIMENTAL APPROACH: Using repeated oral microdoses (30 μg) of the CYP3A index substrate midazolam, we assessed changes in midazolam pharmacokinetics (area under the concentration-time curve from 2-4 h: AUC2-4 and estimated partial metabolic clearance: eClmet ) before, at steady-state, and after discontinuation of 3 x 1000 mg metamizole/d orally for 8 d...
March 22, 2023: British Journal of Clinical Pharmacology