Summary
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/ 106 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 PGF1α (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.
Keywords
Aspirin - Hepatic metabolism - Prostacyclin - Thromboxane
