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Abstract

Selectivity of oral aspirin as an inhibitor of platelet vs. vascular cyclooxygenase activity is reduced by portacaval shunt in rats.

M C Gambino, S Passaghe, Z M Chen, F Bucchi, G Gori, R Latini, G de Gaetano and C Cerletti
Journal of Pharmacology and Experimental Therapeutics April 1988, 245 (1) 287-290;
M C Gambino
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S Passaghe
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Z M Chen
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F Bucchi
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G Gori
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R Latini
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G de Gaetano
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C Cerletti
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Abstract

Oral aspirin can be extensively hydrolyzed to salicylate in the stomach and liver before it enters the systemic circulation. "Presystemic" acetylation of platelets may thus occur during aspirin absorption. This may result in concomitant sparing of peripheral vascular cyclooxygenase mainly exposed to salicylate. We tested whether the "biochemical selectivity" of p.o. aspirin as an inhibitor of platelet rather than vascular cyclooxygenase was reduced by elimination of the "first-pass" hepatic metabolism. A portacaval shunt was inserted in anesthetized rats by connecting the portal vein to the inferior vena cava through a heparinized polyethylene "Y" cannula. Sham-operated rats acted as controls. Ninety minutes after recovery from anesthesia rats were given aspirin p.o. (10 mg/kg) and 45 min later serum thromboxane B2 and 6-keto-prostaglandin F1 alpha formation by vascular rings was evaluated by radioimmunoassay. Serum thromboxane B2 was almost suppressed completely in all animals; vascular 6-ketoprostaglandin F1 alpha was reduced significantly (by 40-60% in aorta and vena cava) in rats with the portacaval shunt but not in sham-operated animals. The results in rats with the shunt were similar to those obtained previously after i.v. aspirin. Fifteen minutes after aspirin, plasma levels of unmetabolized drug measured by high-pressure liquid chromatography were significantly higher in rats with portacaval shunt (0.56 +/- 0.16 micrograms/ml; n = 5) than in sham-operated controls (0.16 +/- 0.02 micrograms/ml; n = 5). These findings support directly the role of first-pass hepatic metabolism in the "biochemical selectivity" of p.o. aspirin.

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Journal of Pharmacology and Experimental Therapeutics
Vol. 245, Issue 1
1 Apr 1988
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Abstract

Selectivity of oral aspirin as an inhibitor of platelet vs. vascular cyclooxygenase activity is reduced by portacaval shunt in rats.

M C Gambino, S Passaghe, Z M Chen, F Bucchi, G Gori, R Latini, G de Gaetano and C Cerletti
Journal of Pharmacology and Experimental Therapeutics April 1, 1988, 245 (1) 287-290;

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Abstract

Selectivity of oral aspirin as an inhibitor of platelet vs. vascular cyclooxygenase activity is reduced by portacaval shunt in rats.

M C Gambino, S Passaghe, Z M Chen, F Bucchi, G Gori, R Latini, G de Gaetano and C Cerletti
Journal of Pharmacology and Experimental Therapeutics April 1, 1988, 245 (1) 287-290;
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