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 (approximately 6 L/kg), consistent with extensive tissue distribution.
Samara
E
E
Abbott Laboratories, Abbott Park, Illinois, USA.
Dutta
S
S
Cao
G
G
Granneman
G R
GR
Dordal
M S
MS
Padley
R J
RJ
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000704:Analysis of Variance; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000187:drug effects; D006207:Half-Life; D006801:Humans; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D010919:Placebos
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010919:Placebos