Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2012;35(12):2112-8.
doi: 10.1248/bpb.b12-00030. Epub 2012 Oct 5.

Theoretical investigation of aspirin dosage regimen to exhibit optimal antiplatelet effects and decrease risk of upper gastrointestinal lesions

Haruko Yokoyama  1 , Takehiro Yaguchi, Yuji Suzuki, Kentaro Tokuoka, Masayuki Watanabe, Yasuhisa Kitagawa, Yasuhiko Yamada
Affiliations
Free article

Theoretical investigation of aspirin dosage regimen to exhibit optimal antiplatelet effects and decrease risk of upper gastrointestinal lesions

Haruko Yokoyama et al. Biol Pharm Bull. 2012.
Free article

Abstract

We investigated dosage regimens for aspirin therapy in regard to antiplatelet effects in patients without gastrointestinal lesions. Findings for inhibition of biosynthesis of thromboxane B(2) (TXB(2)) and prostaglandin E(2) (PGE(2)) were simulated based on pharmacokinetic and pharmacodynamic models using an irreversible process of inhibition of cyclooxygenase-1 (COX-1) by aspirin. We found that the inhibition of biosynthesis of TXB(2) at a steady state was greater than 90% when the dose of aspirin administered exceeded 81 mg, which was considered to exhibit a sufficient antiplatelet effect. Furthermore, it was confirmed that a dose of 162 mg or more is needed to exert an immediate antiplatelet effect on the initial day of administration. On the other hand, the inhibition of biosynthesis of PGE(2) ranged from 40-90% when aspirin was administered at a dose of 10.125-324 mg. Thus, the risk of gastrointestinal lesions differed in a dosage-dependent manner. The biosynthesis inhibition of PGE(2) was calculated to be 37.9%, with that value set as the target level for prevention of gastrointestinal disorders. We also noted a difference between platelets and gastric mucosa cells in regard to the turnover rate of COX-1, and attempted to simulate the inhibition of biosynthesis of TXB(2) and PGE(2) following administration of aspirin. However, it was not possible, as the inhibition of biosynthesis of TXB(2) was greater than 90% and that of PGE(2) was less than 37.9%, even with various dosage regimens. Our findings suggest that it is difficult to determine a rational dosage regimen of aspirin to exert an antiplatelet effect without inducing gastrointestinal lesions.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

MeSH terms