کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8514334 | 1556505 | 2017 | 35 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
R- and S-Warfarin Were Transported by Breast Cancer Resistance Protein: From In Vitro to Pharmacokinetic-Pharmacodynamic Studies
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کلمات کلیدی
Cytochromes P450MDCKIICYP450INRBcrpABCG2HBSSLC-MSPBSMTT - MTTLOD یا Limit of detection - حد تشخیصDrug transport - حمل مواد مخدرABC transporters - حمل کننده ABCLiquid chromatography-mass spectrometry - طیف سنجی جرم کروماتوگرافی مایعMass spectrometry - طیف سنجی جرمیPharmacokinetics/pharmacodynamics - فارماکوکینتیک / فارماکودینامیکPreclinical pharmacokinetics - فارماکوکینتیک پیشکلامیlimit of detection - محدودیت تشخیصHank’s buffered salt solution - محلول نمک بافر هانکPhosphate-buffered saline - محلول نمک فسفات با خاصیت بافریInternational Normalized Ratio - نسبت عادی بین المللیbreast cancer resistance protein - پروتئین مقاومت به سرطان سینه
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: R- and S-Warfarin Were Transported by Breast Cancer Resistance Protein: From In Vitro to Pharmacokinetic-Pharmacodynamic Studies R- and S-Warfarin Were Transported by Breast Cancer Resistance Protein: From In Vitro to Pharmacokinetic-Pharmacodynamic Studies](/preview/png/8514334.png)
چکیده انگلیسی
Warfarin, a racemate of R- and S-warfarin, is an important oral anticoagulant with narrow therapeutic window. Being an acidic drug, warfarin (pKa = 4.94) exists mainly as anion under physiological pH. We hypothesized that the transport of warfarin anion across cell membrane was mediated by breast cancer resistance protein (BCRP), an efflux transporter having a variety of acidic substrates. This study aimed at verifying that warfarin was a substrate of BCRP. Cell lines and mice were used for transport assay and pharmacokinetic-pharmacodynamic studies, respectively. The concentrations of R- and S-warfarin were simultaneously determined by liquid chromatography-mass spectrometry method. Transport assay showed that the intracellular concentrations of R- and S-warfarin in MDCKII-BCRP were significantly lower than those in MDCKII. In addition, Ko143, a potent BCRP inhibitor, significantly inhibited the efflux transport of R- and S-warfarin in MDCKII-BCRP, but not in MDCKII. Pharmacokinetic study showed that the plasma concentrations of R- and S-warfarin in Bcrp-/- mice were significantly higher than those in wild-type mice at 6 h after dosing. Anticoagulation measurement showed that the international normalized ratio in Bcrp-/- mice was significantly higher than that in wild-type mice at 24 h after dosing. In conclusion, R- and S-warfarin were transported by BCRP.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 5, May 2017, Pages 1419-1425
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 5, May 2017, Pages 1419-1425
نویسندگان
Meng-Syuan Yang, Chung-Ping Yu, Pei-Dawn Lee Chao, Shiuan-Pey Lin, Yu-Chi Hou,