Effect of aspirin on protein binding and tissue disposition of oligonucleotide phosphorothioate in rats
Effect of aspirin on protein binding and tissue disposition of oligonucleotide phosphorothioate in rats
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DOI：
10.3109/10611869808995883
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发表时间：
1998-01-01
影响因子：
4.5
通讯作者：
Zhang, RW
中科院分区：
文献类型：
--
作者：
Agrawal, S;Zhang, XS;Zhang, RW
硫代寡核苷酸在动物体内的药代动力学研究表明，静脉给药后，硫代寡核苷酸迅速从血浆中清除，并分布到大多数器官。PS-寡核苷酸广泛与血浆蛋白结合。本研究旨在探讨常用药物阿司匹林对PS-寡核苷酸药代动力学的影响。在本研究中，PS-寡核苷酸被给予灌胃阿司匹林的大鼠。药代动力学研究表明，如果在阿司匹林给药后给药，a)血浆药代动力学参数(t(1/2α)、t(1/2β)、AUC等)。与单独接受PS-寡核苷酸的大鼠相比，动物体内的排泄速度和途径受到影响。这一发现表明，PS寡核苷酸的药代动力学可以受到某些药物的影响，这可能直接影响到PS的生物活性和安全性。
Pharmacokinetic studies of phosphorothioate oligodeoxynucleotides (PS-oligonucleotides) in animals show that following intravenous administration, PS-oligonucleotide clears out rapidly from the plasma and is distributed to majority of the organs. PS-oligonucleotides are bound to plasma proteins extensively. This study was aimed to determine the effect of aspirin, a commonly used drug, on pharmacokinetics of PS-oligonucleotides. In the present study, PS-oligonucleotide was administered to rats that had received aspirin by gavage. Pharmacokinetic study shows that if PS-oligonucleotide was administered following aspirin administration in rats, a) plasma pharmacokinetic parameters (t(1/2 alpha)?, t(1/2 beta), AUC, etc.) had lower values, b) tissue disposition was different, and c) rate and route of elimination was affected in animals compared to rats receiving PS-oligonucleotide alone. This finding suggests that pharmacokinetics of PS oligonucleotides can be affected with certain class of drugs, which may have direct impact on biological activity and safety.