The effects of sitaxentan on sildenafil pharmacokinetics and pharmacodynamics in healthy subjects

Abstract

Aims This study evaluated the effects of sitaxentan on the pharmacodynamic [systemic blood pressure (BP)] and pharmacokinetic (PK) parameters of sildenafil in healthy volunteers. Methods Healthy subjects (18-60 years, n = 24) were randomized into two sequence groups. Group 1 received sitaxentan sodium 100 mg daily (7 days), followed by placebo (7 days). Group 2 received placebo (7 days), followed by sitaxentan sodium 100 mg (7 days). On day 7 of each treatment period, participants received sildenafil 100 mg. PK parameters and BP were analysed on day 7 in each treatment period. Results Sildenafil exposure was slightly higher [AUC∞ geometric mean ratio (GMR), 128%] when co-administered with sitaxentan 100 mg vs. placebo, demonstrating a weak, but statistically significant interaction (90% confidence interval 115.5%, 141.2%). The mean maximum positive (Emax+) and maximum negative (E max-) changes from baseline in both systolic and diastolic BP were comparable for sitaxentan and placebo (range 4.8-7.3 mmHg) with three of four geometric mean ratios falling within the equivalence window, suggesting that the drug interaction was not clinically significant. Adverse events were similar between sitaxentan 100 mg (39%) and placebo (30%). No deaths or serious adverse events occurred during the study. Conclusion The dose of sildenafil does not need to be adjusted when co-administered with sitaxentan. © 2010 The British Pharmacological Society.