کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8513984 | 1556502 | 2017 | 43 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Pretreatment With Rifampicin and Tyrosine Kinase Inhibitor Dasatinib Potentiates the Inhibitory Effects Toward OATP1B1- and OATP1B3-Mediated Transport
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کلمات کلیدی
OATPTris-buffered saline containing 0.05% Tween 20E1SE217βGTBS-TDDIHBSSIC50DMEMAUC - AUCHepatocytes - hepatocytesestrone-3-sulfate - استرون -3 سولفاتhepatic transport - انتقال کبدیCSA - ایالات مؤتلفهٔ آمریکاDrug interactions - تداخل داروییdrug-drug interaction - تعامل دارو و داروDrug transport - حمل مواد مخدرOrganic anion-transporting polypeptide transporters - حمل و نقل پلی پپتید های آنیونی ارگانیزمCyclosporine A - سیکلوسپورینAPharmacokinetics - فارماکوکینتیکMichaelis constant - مایکلز ثابت استarea under the plasma concentration-time curve - محدوده تحت منحنی زمان غلظت پلاسماHanks' balanced salt solution - محلول نمک متعادل هانکسDulbecco’s modified eagle’s medium - محیط عقاب اصلاح شده DulbeccoPhysiologically based pharmacokinetic modeling - مدلسازی فارماکوکینتیک مبتنی بر فیزیولوژیinhibition constant - مهار ثابتorganic anion-transporting polypeptide - پلی اتیلن حمل و نقل آنیونی آلی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Present studies determined the effects of pretreatment with rifampicin, an organic anion-transporting polypeptide (OATP) inhibitor, and the tyrosine kinase inhibitor dasatinib on OATP1B1- and OATP1B3-mediated transport, and evaluated the OATP-mediated drug-drug interaction potential of dasatinib using the static R-value and dynamic physiologically based pharmacokinetic models. Rifampicin and dasatinib pretreatment significantly decreased OATP1B1- and OATP1B3-mediated transport. Rifampicin pretreatment also significantly decreased [3H]-pitavastatin and [3H]-CCK-8 accumulation in human sandwich-cultured hepatocytes. Present studies revealed that estrone-3-sulfate is a less-sensitive OATP1B1 substrate than estradiol-17β-glucuronide in assessing rifampicin pretreatment effects. Pretreatment with rifampicin and dasatinib reduced the inhibition constant (Ki) values against OATP1B1 by 3 and 2.1 fold and against OATP1B3 by 2.4 and 2.1 fold, respectively. The in vitro rifampicin Ki values after preincubation are comparable to the estimated in vivo Ki reported previously. Models predict that dasatinib has a low potential to cause OATP1B1- and OATP1B3-mediated drug-drug interactions. Time-lapse confocal microscopy demonstrated that rifampicin and dasatinib pretreatment did not affect plasma membrane localization of green-fluorescent protein-tagged OATP1B1 (GFP-OATP1B1) and GFP-OATP1B3 in human embryonic kidney 293 stable cell lines. In summary, we report novel findings that pretreatment with rifampicin and dasatinib potentiates the inhibitory effects toward OATP1B1 and OATP1B3 without affecting plasma membrane levels of the transporters.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 8, August 2017, Pages 2123-2135
Journal: Journal of Pharmaceutical Sciences - Volume 106, Issue 8, August 2017, Pages 2123-2135
نویسندگان
Sonia Pahwa, Khondoker Alam, Alexandra Crowe, Taleah Farasyn, Sibylle Neuhoff, Oliver Hatley, Kai Ding, Wei Yue,