Sildenafil given with with ambrisentan, and not bosentan, may be better suited for patients with pulmonary arterial hypertension.
Keiichi Odagiri from the Hamamatsu University School of Medicine in Japan and colleagues found that patients’ plasma concentration of sildenafil was significantly lower if the drug was given in combination with bosentan when compared with ambrisentan.
According to the team, this might be because bosentan induces the expression of cytochrome P450 3A4, which interferes with sildenafil pharmacokinetics. In contrast, ambrisentan has no such effect, so when the seven PAH patients who were enrolled in the study, all taking sildenafil, were switched from bosentan to ambrisentan, their sildenafil plasma concentrations were considerably higher.
The researchers highlighted that the PAH patients in the cohort received bosentan at a dose of 62.5 mg twice a day, instead of the typically recommended dose of 125 mg. twice a day. The Japanese doctors used this dose, as they explained in a news release, “because of concerns about dose-dependent hepatic toxicity, even though the pharmacokinetics of bosentan and its metabolites are broadly comparable in Japanese and Caucasian individuals.”
The team reported that exercise tolerance was significantly better during treatment with sildenafil in combination with ambrisentan than during treatment with sildenafil plus bosentan. The median distance achieved in the externally paced 10-meter shuttle walking test was higher during the four to five weeks of treatment with ambrisentan compared to bosentan (340 vs. 280 meters, respectively).