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

Publication ,  Journal Article
de Denus, S; Rouleau, JL; Mann, DL; Huggins, GS; Pereira, NL; Shah, SH; Cappola, TP; Fouodjio, R; Mongrain, I; Dubé, M-P
Published in: Pharmacogenomics J
April 2018

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.

Duke Scholars

Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

April 2018

Volume

18

Issue

2

Start / End Page

232 / 237

Location

United States

Related Subject Headings

  • Vasodilator Agents
  • Stroke Volume
  • Sildenafil Citrate
  • Pharmacology & Pharmacy
  • Middle Aged
  • Male
  • Humans
  • Heart Failure
  • Genotype
  • Female
 

Citation

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de Denus, S., Rouleau, J. L., Mann, D. L., Huggins, G. S., Pereira, N. L., Shah, S. H., … Dubé, M.-P. (2018). CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction. Pharmacogenomics J, 18(2), 232–237. https://doi.org/10.1038/tpj.2017.8
Denus, S. de, J. L. Rouleau, D. L. Mann, G. S. Huggins, N. L. Pereira, S. H. Shah, T. P. Cappola, R. Fouodjio, I. Mongrain, and M. -. P. Dubé. “CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction.Pharmacogenomics J 18, no. 2 (April 2018): 232–37. https://doi.org/10.1038/tpj.2017.8.
de Denus S, Rouleau JL, Mann DL, Huggins GS, Pereira NL, Shah SH, et al. CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction. Pharmacogenomics J. 2018 Apr;18(2):232–7.
de Denus, S., et al. “CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction.Pharmacogenomics J, vol. 18, no. 2, Apr. 2018, pp. 232–37. Pubmed, doi:10.1038/tpj.2017.8.
de Denus S, Rouleau JL, Mann DL, Huggins GS, Pereira NL, Shah SH, Cappola TP, Fouodjio R, Mongrain I, Dubé M-P. CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction. Pharmacogenomics J. 2018 Apr;18(2):232–237.

Published In

Pharmacogenomics J

DOI

EISSN

1473-1150

Publication Date

April 2018

Volume

18

Issue

2

Start / End Page

232 / 237

Location

United States

Related Subject Headings

  • Vasodilator Agents
  • Stroke Volume
  • Sildenafil Citrate
  • Pharmacology & Pharmacy
  • Middle Aged
  • Male
  • Humans
  • Heart Failure
  • Genotype
  • Female