Theoretical Investigation of Aspirin Dosage Regimen to Exhibit Optimal Antiplatelet Effects and Decrease Risk of Upper Gastrointestinal Lesions
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概要
- 論文の詳細を見る
We investigated dosage regimens for aspirin therapy in regard to antiplatelet effects in patients without gastrointestinal lesions. Findings for inhibition of biosynthesis of thromboxane B2 (TXB2) and prostaglandin E2 (PGE2) 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 TXB2 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 PGE2 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 PGE2 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 TXB2 and PGE2 following administration of aspirin. However, it was not possible, as the inhibition of biosynthesis of TXB2 was greater than 90% and that of PGE2 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.
- 公益社団法人 日本薬学会の論文
著者
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Yokoyama Haruko
Department Of Biomaterials Institute For Frontier Medical Sciences Kyoto University
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Yamada Yasuhiko
Department Of Clinical Evaluation Of Drug Efficacy School Of Pharmacy Tokyo University Of Pharmacy A
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Tokuoka Kentaro
Department Of Medicine Tokai University School Of Medicine
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Kitagawa Yasuhisa
Department Of Internal Medicine Division Of Neurology Tokai University School Of Medicine
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Watanabe Masayuki
Department Of Biology Graduate School Of Natural Science Konan University
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Suzuki Yuji
Department Of Astronomy Kyoto University
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Yokoyama Haruko
Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Yaguchi Takehiro
Department of Clinical Evaluation of Drug Efficacy, School of Pharmacy, Tokyo University of Pharmacy and Life Sciences
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Tokuoka Kentaro
Departments of Neurology, Tokai University of Hachioji Hospital
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SUZUKI Yuji
Department of Agriculture, Graduate School of Agricultural Science, Tohoku University
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Suzuki Yuji
Departments of Pharmacy, Tokai University of Hachioji Hospital
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