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. Warfarin anticoagulation therapy is common for patients with PAH. When coadministered, sulfonamide-class ERAs have been shown to induce (bosentan) or inhibit (sitaxsentan) the p450-dependent metabolism of warfarin and alter the pharmacokinetic (PK) and pharmacodynamic (PD) effects of warfarin. Therefore, the potential for ambrisentan to affect the PK or PD of warfarin was examined.
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