Open AccessPharmacokinetic and Pharmacodynamic Comparison of Sildenafil‐Bosentan and Sildenafil‐Ambrisentan Combination Therapies for Pulmonary Hypertension
Author(s) -
Hakamata A,
Odagiri K,
Miyakawa S,
Irisawa H,
Takeuchi K,
Inui N,
Tanaka S,
Uchida S,
Watanabe H
Publication year - 2016
Publication title -
clinical and translational science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.303
H-Index - 44
eISSN - 1752-8062
pISSN - 1752-8054
DOI - 10.1111/cts.12382
Subject(s) - sildenafil , bosentan , ambrisentan , medicine , pharmacokinetics , pharmacodynamics , pulmonary hypertension , pharmacology , urology , tadalafil , endothelin receptor , receptor
To elucidate whether the pharmacokinetics (PK) and pharmacodynamics (PD) of sildenafil are influenced differently when it is coadministered with bosentan (S+B) or with ambrisentan (S+A), we evaluated the PK and PD profiles of sildenafil before and after 4–5 weeks of S+A or S+B treatment in patients with pulmonary arterial hypertension. The area under the plasma concentration–time curve of sildenafil was significantly higher in S+A treatment than in S+B treatment (165.8 ng•h/mL vs. 396.8 ng•h/mL, P = 0.018) and the oral clearance of sildenafil was significantly lower after S+A treatment than after S+B treatment (120.6 L/h/kg vs. 50.4 L/h/kg, P = 0.018). In the PD study, incremental shuttle walking distance was superior during treatment with S+A than during treatment with S+B (S+B; 280 m vs. S+A; 340 m, P = 0.042). There were no concerns about safety with either combination therapy regime.