CYP450 activity, drug interactions, and genetic polymorphisms: clinical relevance for the new selective cardiac myosin inhibitors
Both mavacamten and aficamten exhibit complex disposition and are extensively metabolized by CYP450 isoenzymes including CYP2C9, CYP2C19, and CYP2D6, which exhibit genetic polymorphisms. CYP3A4 contributes less to the metabolism of mavacamten and aficamten. However, CYP3A4 can influence the disposition of these CMIs and other drugs, as CYP3A4 is subjected to induction and inhibition, and modulation by inflammatory factors. Therefore, multi-drug interactions due to changes in the metabolic clearances of CMIs are expected in HCM patients with other chronic conditions and polypharmacy.
Authors
- Milind Y. Desai (ORCID: https://orcid.org/0000-0003-0010-9797)
- ANJALI TIKU OWENS (ORCID: https://orcid.org/0000-0002-9669-8495)
- Michelle Michels
- Matthew L. Arwood (ORCID: https://orcid.org/0000-0003-4737-9786)
- Pamela Dow (ORCID: https://orcid.org/0000-0002-9983-8545)
- Jacques Turgeon (ORCID: https://orcid.org/0000-0002-7978-9280)
- Véronique Michaud (ORCID: https://orcid.org/0000-0002-1399-6447)
- Matthew W Martinez (ORCID: https://orcid.org/0000-0001-9255-4657)
- David Thacker
Institutions
- Cleveland Clinic (US)
- Erasmus MC (NL)
- California University of Pennsylvania (US)
- Galen Research (United Kingdom) (GB)
- Galena Biopharma (United States) (US)
- Atlantic Health System (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Expert Opinion on Drug Safety
- Published
- 2025-11-28
- DOI
- https://doi.org/10.1080/14740338.2025.2596231
- Primary Topic
- Eicosanoids and Hypertension Pharmacology
- Type
- article
- Field-Weighted Citation Impact
- 0.00