Extrahepatic metabolism and distribution of aspirin in vascular beds of sheep.
The dispositions of aspirin, its metabolite, salicylic acid, and its subsequent metabolite, salicyluric acid, were studied in eight anesthetized sheep infused with aspirin (61 and 485 microgram X min-1 X kg-1) for 75 min. Plasma samples were withdrawn from the portal vein, hepatic vein, pulmonary artery, left ventricle, left femoral vein, and left femoral artery. Significant extraction of aspirin occurred across the liver and hind leg, with mean availabilities of 0.75, 0.98, and 0.82 observed across the liver, lung, and hind leg, respectively. The extraction of aspirin was not affected by coadministration of sodium salicylate (30-1200 mg equiv salicylic acid). This extraction reflected hydrolysis of aspirin to salicylic acid; the metabolism of aspirin in the hind leg, lung, and liver being confirmed with tissue homogenate studies. The metabolism of aspirin in the extrahepatic tissues is significant in relation to the proposed selective presystemic acetylation of platelet cyclooxygenase by aspirin and the use of low-dose aspirin for thrombotic indications.
D000818:Animals; D001241:Aspirin / Q000097:blood / Q000378:metabolism*; D006614:Hindlimb / Q000098:blood supply; D007700:Kinetics; D011485:Protein Binding; D012756:Sheep
D001241:Aspirin