Single‐Dose Pharmacokinetics of Atrasentan, an Endothelin‐A Receptor Antagonist

The pharmacokinetics of 1, 10, 23.25, and 139.5 mg doses of atrasentan was assessed in a placebo‐controlled, double‐blind, single oral dose study in 24 healthy male subjects. Atrasentan was well tolerated. Atrasentan pharmacokinetics was linear in the 1 to 23.25 mg dose range, with some dose dependency in the highest dose group. Harmonic mean terminal half‐life was similar across all dose groups (20–25 h). Apparent oral clearance was low (12 L/h) for the highest dose group compared with the other three dose groups (21–27 L/h). The apparent volume of distribution was large (∼6 L/kg), consistent with extensive tissue distribution.