Abstract
PURPOSE: Ambrisentan is a high affinity, propanoic acid-class, ETA-selective endothelin receptor antagonist (ERA). Ambrisentan doses of 2.5 and 5 mg once-daily have been shown to improve 6-minute walk distance and delay clinical worsening in a placebo-controlled study (ARIES-2) of patients with pulmonary arterial hypertension (PAH), with no incidence of serum aminotransferases >3xULN. Sildenafil is a phosphodiesterase type 5 inhibitor approved for PAH. Coadministration of sulfonamide-class ERAs have been shown to decrease (bosentan) or increase (sitaxsentan) the systemic exposure (AUC) of sildenafil, while sildenafil has been shown to increase the AUC of bosentan. Therefore, the potential for pharmacokinetic (PK) interactions between ambrisentan and sildenafil were examined.
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