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 2 4 healthy male subjects. Atrasentan was well tolerated. Atrasentan pharmaco kinetics was linear in the I to 23.25 mg dose range, with some dose depende ncy in the highest dose group. Harmonic mean termi-nal half-life was simila r 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 (similar to 6L/kg), consistent with extensive tissue distribution. (C) 2001 the American Colleg e of Clinical Pharmacology.