Impact of amiodarone use on metoprolol concentrations, α-OH-metoprolol concentrations, metoprolol dosing and heart rate: A cross-sectional study.

Autor: Robert S; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada., Pilon MO; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada., Oussaïd E; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada., Meloche M; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada., Leclair G; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada., Jutras M; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada., Gaulin MJ; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada., Mongrain I; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada., Busseuil D; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada., Tardif JC; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.; Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada., Dubé MP; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.; Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada., de Denus S; Faculty of Pharmacy, Université de Montréal, Montreal, Quebec, Canada.; Montreal Heart Institute, Montreal, Quebec, Canada.; Université de Montreal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
Jazyk: angličtina
Zdroj: Pharmacology research & perspectives [Pharmacol Res Perspect] 2023 Oct; Vol. 11 (5), pp. e01137.
DOI: 10.1002/prp2.1137
Abstrakt: Small studies suggest that amiodarone is a weak inhibitor of cytochrome P450 (CYP) 2D6. Inhibition of CYP2D6 leads to increases in concentrations of drugs metabolized by the enzyme, such as metoprolol. Considering that both metoprolol and amiodarone have β-adrenergic blocking properties and that the modest interaction between the two drugs would result in increased metoprolol concentrations, this could lead to a higher risk of bradycardia and atrioventricular block. The primary objective of this study was to evaluate whether metoprolol plasma concentrations collected at random timepoints from patients enrolled in the Montreal Heart Institute Hospital Cohort could be useful in identifying the modest pharmacokinetic interaction between amiodarone and metoprolol. We performed an analysis of a cross-sectional study, conducted as part of the Montreal Heart Institute Hospital Cohort. All participants were self-described "White" adults with metoprolol being a part of their daily pharmacotherapy regimen. Of the 999 patients being treated with metoprolol, 36 were also taking amiodarone. Amiodarone use was associated with higher metoprolol concentrations following adjustment for different covariates (p = .0132). Consistently, the association between amiodarone use and lower heart rate was apparent and significant after adjustment for all covariates under study (p = .0001). Our results highlight that single randomly collected blood samples can be leveraged to detect modest pharmacokinetic interactions.
(© 2023 The Authors. Pharmacology Research & Perspectives published by British Pharmacological Society and American Society for Pharmacology and Experimental Therapeutics and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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