• Skip to primary navigation
  • Skip to main content
  • Skip to footer
Invitae | Genelex

Invitae | Genelex

Pharmacogenetics Makes Precision Medicine Possible

  • For Patients
    • Conditions
    • Affected Drugs
    • What is PGx?
    • Resources
    • FAQs
  • For Providers
    • Conditions
    • Resources
    • Order Testing Supplies
  • Test Menu
  • Clinical Trials
  • About
    • Lab Accreditations
    • Genelex Team
    • Contact Us
  • Log In

Pharmacokinetic Interaction Between Tadalafil and Bosentan in Healthy Male Subjects

Home / Data / Pharmacokinetic Interaction Between Tadalafil and Bosentan in Healthy Male Subjects

Genelex Blog

Pharmacokinetic Interaction Between Tadalafil and Bosentan in Healthy Male Subjects

COMMENT: Combinations of agents are being tried for pulmonary arterial hypertension (PAH)- a serious illness with a limited life expectancy. The clinical study below shows that the combination of a PDE5 inhibitor, tadalafil with bosentan, an agent already in use for PAH leads to the significant reduction in exposure of tadalafil because of the induction of CYP3A4 by bosentan.

 

ABSTRACT: Clin Pharmacol. 2008 Feb 27 Pharmacokinetic Interaction Between Tadalafil and Bosentan in Healthy Male Subjects. Wrishko RE, Dingemanse J, Yu A, Darstein C, Phillips DL, Mitchell MI. Lilly Research Laboratories.

Tadalafil, an oral phosphodiesterase 5 (PDE5) inhibitor, is being investigated as a treatment for pulmonary arterial hypertension. Bosentan is an oral endothelin receptor antagonist widely used in the treatment of pulmonary arterial hypertension.Tadalafil is mainly metabolized by cytochrome P450 (CYP) 3A4, and as bosentan induces CYP2C9 and CYP3A4, a pharmacokinetic interaction is possible between these agents. This open-label, randomized study investigated whether any pharmacokinetic interaction exists between tadalafil and bosentan. Healthy adult men (n = 15; 19-52 years of age) received 10 consecutive days of tadalafil 40 mg once daily, bosentan 125 mg twice daily, and a combination of both in a 3-period, crossover design. Following 10 days of multiple-dose coadministration of bosentan and tadalafil, compared with tadalafil alone, tadalafil geometric mean ratios (90% confidence interval [CI]) for AUCtau and Cmax were 0.59 (0.55, 0.62) and 0.73 (0.68, 0.79), respectively, with no observed change in tmax. Following coadministration of bosentan with tadalafil, bosentan ratios (90% CI) for AUCtau and Cmax were 1.13 (1.02, 1.24) and 1.20 (1.05, 1.36), respectively. Tadalafil alone and combined with bosentan was generally well tolerated. In conclusion, after 10 days of coadministration, bosentan decreased tadalafil exposure by 41.5% with minimal and clinically irrelevant differences (<20%) in bosentan exposure.

PMID: 18305126

Genelex Resources

Affected Conditions
Affected Drugs
Info for Providers
Frequently Asked Questions
Contact Genelex
Join Our Mailing List

Footer

CONTACT US

(800) 837-8362
info@genelex.com

3101 Western Ave.
Suite 100
Seattle, WA 98121

HELPFUL INFORMATION

What is PGx?
Test Menu
Conditions
Affected Drugs
FAQs
References

ABOUT GENELEX

Blog
News
Genelex Team
Lab Accreditations
Contact Us
Privacy Practices
Privacy Policy

  • Facebook
  • LinkedIn
  • RSS
  • Twitter
  • YouTube

KEEP IN TOUCH

Stay in the loop with news and updates from Genelex and be among the first to know when new tests become available.