Oral bioavailability and disposition characteristics of irbesartan, an angiotensin antagonist, in healthy volunteers.
Absolute oral bioavailability and disposition characteristics of irbesartan, an angiotensin II receptor antagonist, were investigated in 18 healthy young male volunteers. Subjects received [14C] irbesartan as a 30-minute intravenous infusion (50 mg), [14C] irbesartan orally as a solution (50 mg or 150 mg), or irbesartan capsule (50 mg). Irbesartan was rapidly and almost completely absorbed after oral administration, and exhibited a mean absolute oral bioavailability of 60% to 80%. Mean total body clearance was approximately 157 mL/min, and renal clearance was 3.0 mL/min. Volume of distribution at steady state was 53 L to 93 L, and terminal elimination half-life was approximately 13 to 16 hours. Hepatic extraction ratio was low (0.2). There were no major circulating metabolites, and approximately 80% of total plasma radioactivity was attributable to unchanged irbesartan. Regardless of route of administration, approximately 20% of dose was recovered in urine and the remainder in feces.
Vachharajani
N N
NN
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey 08540, USA.
Shyu
W C
WC
Chando
T J
TJ
Everett
D W
DW
Greene
D S
DS
Barbhaiya
R H
RH
D000284:Administration, Oral; D000328:Adult; D000804:Angiotensin II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D019540:Area Under Curve; D001682:Biological Availability; D001713:Biphenyl Compounds / Q000009:adverse effects / Q000493:pharmacokinetics*; D018592:Cross-Over Studies; D006207:Half-Life; D006801:Humans; D000077405:Irbesartan; D008297:Male; D013777:Tetrazoles / Q000009:adverse effects / Q000493:pharmacokinetics*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D013777:Tetrazoles; D000804:Angiotensin II; D000077405:Irbesartan