CYP3A4 genotype is associated with sildenafil concentrations in patients with heart failure with preserved ejection fraction.
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
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- Vasodilator Agents
- Stroke Volume
- Sildenafil Citrate
- Pharmacology & Pharmacy
- Middle Aged
- Male
- Humans
- Heart Failure
- Genotype
- Female
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Vasodilator Agents
- Stroke Volume
- Sildenafil Citrate
- Pharmacology & Pharmacy
- Middle Aged
- Male
- Humans
- Heart Failure
- Genotype
- Female