کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486090 | 1114374 | 2010 | 19 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Evidence of carrierâmediated transport in the penetration of donepezil into the rat brain
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
The objective of this study was to characterize the mechanism that controls the transport of donepezil into the brain. The apparent brain uptake clearance (CLapp,br) was decreased as a function of the dose of donepezil, suggesting an involvement of a saturable transport process via transporter(s) in the penetration across the blood-brain barrier (BBB). Consistent with in vivo results, the uptake of substrates for organic cation transporters was significantly reduced by donepezil in both MBEC4 cells (i.e., a model for BBB) and HEK 293 cells expressing the transporters found in the brain, indicative of the involvement of organic cation transporters in the transport of the drug. Furthermore, donepezil transport was enhanced (pâ<â0.01) in HEK 293 cells expressing rOCNT1, rOCTN2, or rCHT1. The CLapp,br was reduced up to 52.8% of the control in rats that had been pretreated with choline, while the CLapp,br was unaffected with pretreatments with organic cations other than choline, suggesting that choline and donepezil share a common transport mechanism in the penetration across the BBB in vivo. Taken together, these observations suggest that the transport of donepezil across the BBB is mediated by organic cation transporters such as choline transport system(s). © 2009 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 99: 1548-1566, 2010
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 3, March 2010, Pages 1548-1566
Journal: Journal of Pharmaceutical Sciences - Volume 99, Issue 3, March 2010, Pages 1548-1566
نویسندگان
MiâHwa Kim, HanâJoo Maeng, KyungâHa Yu, KyeongâRyoon Lee, Takashi Tsuruo, DaeâDuk Kim, ChangâKoo Shim, SukâJae Chung,