Measurement of Aspirin Concentrations in Portal and Systemic Blood in Pigs: Effect on Platelet Aggregation, Thromboxane and Prostacyclin Production

Abstract

Low doses of enteric-coated aspirin were administered orally to pigs. Plasma aspirin concentrations measured in blood obtained simultaneously from permanent catheters in a systemic artery and portal vein for 6 hours after dosage showed a large variation in the plasma aspirin concentration: time profile between pigs. After 50 mg single dose the ratio of the arterial: portal area under the plasma concentration versus time curve (AUC) was 0.63 +/- 0.08 (mean +/- SE, n = 6). In three pigs which received all three dosage regimens, the arterial: portal AUC ratios were 0.48 +/- 0.05 after 50 mg single dose, 0.52 +/- 0.02 after 100 mg single dose and 0.47 +/- 0.02 after 100 mg daily for 1 week. Platelet aggregation in response to sodium arachidonate (1.65 mM) was completely abolished after chronic aspirin administration of 100 mg daily. Thromboxane production (pg/10(6) platelets) induced by this stimulus decreased from 536 +/- 117 before aspirin to 57 +/- 14 after aspirin (mean +/- SE, n = 4; p = 0.03). Aortic prostacyclin synthesis, measured as 6-keto PGF1 alpha (ng/disc after 10 min incubation), was 1.66 +/- 0.28 (mean +/- SE, n = 4) in untreated pigs and 0.95 +/- 0.25 (n = 5) in treated pigs (p = 0.07). Results from this study support the idea that a difference between aspirin concentrations in the portal and systemic circulations can be achieved. Whether this can be translated into a clinically useful differential effect on the vessel wall compared to the platelet remains to be determined.