کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8513304 | 1556492 | 2018 | 41 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Inhibition of Organic Anion Transporting Polypeptide 1B1 and 1B3 by Betulinic Acid: Effects of Preincubation and Albumin in the Media
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کلمات کلیدی
CysADDIsFBSATVDcfDPBS2′,7′-dichlorofluorescein - 2 '، 7'-dichlorofluoresceinBSA - BSALC-MS/MS - LC-MS / MSAtorvastatin - آتورواستاتینbovine serum albumin - آلبومین سرم گاوUrsolic acid - اسید اورسولیکOleanolic acid - اسید اولانیولیکBetulinic acid - اسید بتولینیکDrug interactions - تداخل داروییdrug-drug interactions - تعاملات داروییFood interactions - تعاملات غذاییDrug transport - حمل مواد مخدرTransporters - حمل و نقلfetal bovine serum - سرم جنین گاوcyclosporin A - سیکلوسپورین Aliquid chromatography tandem-mass spectrometry - طیف سنجی جرمی کروماتوگرافی مایعNatural products - فرآورده های طبیعیDulbecco's phosphate-buffered saline - فسفات باسیل نمک Dulbecco
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Betulinic acid (BA), a plant-derived pentacyclic triterpenoid, may interact with the members of the organic anion transporting polypeptide 1B subfamily. Here, we investigated the interactions of BA and its analogs with OATP1B1/3 and rat Oatp1b2 in vitro and in vivo. BA inhibited the activity of OATP1B1/3 and rat Oatp1b2 in vitro. Systemic exposure of atorvastatin was substantially altered with the intravenous co-administration of BA (20 mg/kg). Preincubation (incubation with inhibitors, followed by washout) with BA led to a sustained inhibition of OATP1B3, which recovered rapidly in the media containing 10% fetal bovine serum. The addition of albumin to the media decreased intracellular concentrations of BA and expedited the recovery of OATP1B3 activity following preincubation. For asunaprevir and cyclosporin A (previously known to inhibit OATP1B3 upon preincubation), the addition of albumin to the media shortened recovery time with asunaprevir, but not with cyclosporin A. Overall, our results showed that BA inhibits OATP1B transporters in vitro and may incur hepatic transporter-mediated drug interactions in vivo. Our results identify BA as another OATP1B3 inhibitor with preincubation effect and suggest that the preincubation effect and its duration is impacted by altered equilibrium of inhibitors between intracellular and extracellular space (e.g., albumin in the media).
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 107, Issue 6, June 2018, Pages 1713-1723
Journal: Journal of Pharmaceutical Sciences - Volume 107, Issue 6, June 2018, Pages 1713-1723
نویسندگان
Yunseok Oh, Yoo-Seong Jeong, Min-Soo Kim, Jee Sun Min, Gongmi Ryoo, Ji Eun Park, Yearin Jun, Yoo-Kyung Song, Se-Eun Chun, Songhee Han, Soo Kyung Bae, Suk-Jae Chung, Wooin Lee,