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Thromb Haemost 1989; 61(02): 211-216
DOI: 10.1055/s-0038-1646561
Original Article
Schattauer GmbH Stuttgart

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

F Bochner
1   The Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia, Australia
,
D M Siebert
1   The Department of Clinical and Experimental Pharmacology, University of Adelaide, South Australia, Australia
,
S E Rodgers
2   The Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia
,
G H McIntosh
3   The C. S. I. R. O. Division of Human Nutrition, Glenthorne Laboratory O’Halloran Hill, South Australia, Australia
,
M J James
4   The Department of Surgeny, Flinders Medical Centre, Adelaide, South Australia, Australia
,
J V Lloyd
2   The Division of Haematology, Institute of Medical and Veterinary Science, Adelaide, South Australia, Australia
› Author Affiliations
Further Information

Publication History

Received 30 August 1988

Accepted after revision 06 December 1988

Publication Date:
30 June 2018 (online)

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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
 

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