Agrawal S, Zhang X, Cai Q, Kandimalla E R, Manning A, Jiang Z, Marcel T, Zhang R
Hybridon, Inc., Cambridge, MA 02139, USA.
J Drug Target. 1998;5(4):303-12. doi: 10.3109/10611869808995883.
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 (t1/2alpha?, t1/2beta, 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.
硫代磷酸酯寡脱氧核苷酸（PS - 寡核苷酸）在动物体内的药代动力学研究表明，静脉给药后，PS - 寡核苷酸迅速从血浆中清除，并分布到大多数器官。PS - 寡核苷酸与血浆蛋白广泛结合。本研究旨在确定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，将PS - 寡核苷酸给予经灌胃给予阿司匹林的大鼠。药代动力学研究表明，如果在大鼠中先给予阿司匹林后再给予PS - 寡核苷酸，a）血浆药代动力学参数（t1/2α、t1/2β、AUC等）值较低，b）组织分布不同，c）与单独接受PS - 寡核苷酸的大鼠相比，动物的消除速率和途径受到影响。这一发现表明，PS - 寡核苷酸的药代动力学可能会受到某些类药物的影响，这可能对其生物活性和安全性产生直接影响。
