Format

Send to

Choose Destination
Pharmacogenomics J. 2018 Apr;18(2):232-237. doi: 10.1038/tpj.2017.8. Epub 2017 Apr 25.

CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction.

Author information

1
Research Center, Montreal Heart Institute, Montreal, Quebec, Canada.
2
Université de Montréal Beaulieu-Saucier Pharmacogenomics Center, Montreal, Quebec, Canada.
3
Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada.
4
Faculty of Medicine, Université de Montréal, Montreal, Quebec, Canada.
5
Department of Medicine, Washington University School of Medicine, St. Louis, MO, USA.
6
Molecular Cardiology Research Institute Center for Translational Genomics, Tufts Medical Center, Boston, MA, USA.
7
Division of Cardiovascular Diseases, Division of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Rochester, MN, USA.
8
Division of Cardiology, Duke University School of Medicine, Durham, NC, USA.
9
Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA, USA.

Abstract

Despite its established inter-individual variability, sildenafil has been the subject of only a few pharmacogenetic investigations, with limited data regarding the genetic modulators of its pharmacokinetics. We conducted a pharmacogenetic sub-study of patients randomized to sildenafil (n=85) in the RELAX trial, which investigated the impact of high-dose sildenafil in patients with heart failure with preserved left ventricular ejection fraction (HFpEF). In the overall population, the CYP3A4 inferred phenotype appeared associated with the dose-adjusted peak concentrations of sildenafil at week 12 and week 24 (adjusted P=0.045 for repeated measures analysis), although this P-value did not meet our corrected significance threshold of 0.0167. In the more homogeneous Caucasian subgroup, this association was significant (adjusted P=0.0165 for repeated measures). Hence, CYP3A4 inferred phenotype is associated with peak sildenafil dose-adjusted concentrations in patients with HFpEF receiving high doses of sildenafil. The clinical impact of this association requires further investigation.

PMID:
28440343
PMCID:
PMC5656562
DOI:
10.1038/tpj.2017.8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center