کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486200 | 1114377 | 2011 | 13 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Sodium fluorescein is a probe substrate for hepatic drug transport mediated by OATP1B1 and OATP1B3
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
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چکیده انگلیسی
The aim of this study was to characterize the in vitro hepatic uptake kinetics of sodium fluorescein (NaFluo) and identify the transporters involved. NaFluo exhibited saturable uptake kinetics in suspended rat and human hepatocytes as reflected by Km values of 22.5 and 14.1 µM, and Vmax values of 98.3 and 5.8 pmol/(million cells
- min), respectively. Coincubation with known inhibitors (e.g. rifampicin) of organic anion transporting polypeptide (OATP/Oatp; SLCO gene family) significantly decreased NaFluo uptake in hepatocytes. In contrast, neither inhibitors/substrates of the organic cation transporter or organic anion transporter family nor depletion of extracellular sodium resulted in significant inhibition of NaFluo uptake. To explore the contribution of individual uptake transporters, NaFluo uptake was determined in Chinese hamster ovary cells transfected with OATP1B1, OATP1B3, and OATP2B1. Transporterâmediated uptake of NaFluo was observed in OATP1B1â and OATP1B3âtransfected cells (Km = 4.2 and 10.9 µM; Vmax = 30.9 and 135 [pmol/(mg protein
- min)], respectively). NaFluo can be used as a probe substrate to study Oatp/OATP1Bâmediated drug interactions in fluorescenceâbased in vitro transport assays of rat and human liver. Labeling of drugs or bile salts with a fluorescein moiety can be expected to result in fluorescent conjugates with substantially altered hepatic uptake characteristics as compared with the unconjugated compounds. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:5018-5030, 2011
- min), respectively. Coincubation with known inhibitors (e.g. rifampicin) of organic anion transporting polypeptide (OATP/Oatp; SLCO gene family) significantly decreased NaFluo uptake in hepatocytes. In contrast, neither inhibitors/substrates of the organic cation transporter or organic anion transporter family nor depletion of extracellular sodium resulted in significant inhibition of NaFluo uptake. To explore the contribution of individual uptake transporters, NaFluo uptake was determined in Chinese hamster ovary cells transfected with OATP1B1, OATP1B3, and OATP2B1. Transporterâmediated uptake of NaFluo was observed in OATP1B1â and OATP1B3âtransfected cells (Km = 4.2 and 10.9 µM; Vmax = 30.9 and 135 [pmol/(mg protein
- min)], respectively). NaFluo can be used as a probe substrate to study Oatp/OATP1Bâmediated drug interactions in fluorescenceâbased in vitro transport assays of rat and human liver. Labeling of drugs or bile salts with a fluorescein moiety can be expected to result in fluorescent conjugates with substantially altered hepatic uptake characteristics as compared with the unconjugated compounds. © 2011 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 100:5018-5030, 2011
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 11, November 2011, Pages 5018-5030
Journal: Journal of Pharmaceutical Sciences - Volume 100, Issue 11, November 2011, Pages 5018-5030
نویسندگان
Tom De Bruyn, Sarinj Fattah, Bruno Stieger, Patrick Augustijns, Pieter Annaert,