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

Journal Article (Journal Article;Multicenter Study)

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.

Full Text

Duke Authors

Cited Authors

  • de Denus, S; Rouleau, JL; Mann, DL; Huggins, GS; Pereira, NL; Shah, SH; Cappola, TP; Fouodjio, R; Mongrain, I; Dubé, M-P

Published Date

  • April 2018

Published In

Volume / Issue

  • 18 / 2

Start / End Page

  • 232 - 237

PubMed ID

  • 28440343

Pubmed Central ID

  • PMC5656562

Electronic International Standard Serial Number (EISSN)

  • 1473-1150

Digital Object Identifier (DOI)

  • 10.1038/tpj.2017.8


  • eng

Conference Location

  • United States