کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2485044 | 1114343 | 2013 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pharmacokinetics of Vicagrel, a Promising Analog of Clopidogrel, in Rats and Beagle Dogs
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Pharmacokinetics of Vicagrel, a Promising Analog of Clopidogrel, in Rats and Beagle Dogs Pharmacokinetics of Vicagrel, a Promising Analog of Clopidogrel, in Rats and Beagle Dogs](/preview/png/2485044.png)
چکیده انگلیسی
The objective of this investigation was to compare the efficiency of conversion to the active metabolite (AM) from clopidogrel and vicagrel, a novel antiplatelet agent, and support the drug design rationale in the view of the pharmacokinetics. Following intravenous administration to rats, vicagrel was rapidly converted to its thiolactone intermediate (2-oxo-clopidogrel), then to the AM. The transformation efficiency of vicagrel to 2-oxo-clopidogrel was 94%, but only 13% of clopidogrel was converted to 2-oxo-clopidogrel. Compared with the clopidogrel following oral administration to rats and beagle dogs at equal molar doses, vicagrel increased the exposure to 2-oxo-clopidogrel approximately sixfold (58.6 ± 10.2 vs. 10.2 ± 6.6 µg h/L in rats, 97.1 ± 51.9 vs. 16.1 ± 3.3 µg h/L in dogs) and the exposure to the AM approximately fourfold to sixfold (59.0 ± 18.8 vs. 14.4 ± 9.6 µg h/L in rats, 635.1 ± 114.5 vs. 99.0 ± 10.3 µg h/L in dogs). The rapid and extensive conversion of vicagrel to the intermediate 2-oxo-clopidogrel by esterase instead of cytochrome P450s (CYPs) makes the novel prodrug vicagrel a promising agent to prevent platelet aggregation and overcome clopidogrel resistance and high interindividual variability due to CYP2C19 polymorphism.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 2, February 2013, Pages 741-749
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 2, February 2013, Pages 741-749
نویسندگان
Zhixia Qiu, Ning Li, Xin Wang, Fengjie Tian, Qi Liu, Ling Song, Zhen Fan, Yang Lu, Xijing Chen,