کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2487645 | 1114424 | 2007 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Disposition of the cholesterol absorption inhibitor ezetimibe in mdr1a/b (â/â) mice
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کلمات کلیدی
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
اکتشاف دارویی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Disposition of the cholesterol absorption inhibitor ezetimibe in mdr1a/b (â/â) mice Disposition of the cholesterol absorption inhibitor ezetimibe in mdr1a/b (â/â) mice](/preview/png/2487645.png)
چکیده انگلیسی
The lipid lowering agent ezetimibe (EZ) and its intestinally formed glucuronide (GLUC) were shown to be substrates of the efflux transporters Pâglycoprotein (Pâgp) and the multidrug resistance associated protein 2 (MRP2) which markedly influences the disposition and efficacy of EZ in man. This study aims to elucidate the unique meaning of Pâgp in the pharmacokinetics of EZ in mice. In brief, serum concentrations, organ distribution and elimination of EZ were determined in 10 male wildâtype and mdr1a/b (â/â) mice after oral treatment with EZ (10 mg/kg, 10 days). EZ and GLUC were quantified in serum, urine, feces and various tissues using a validated LCâMS/MS method. Compared to wildâtype mice, mdr1a/b knockout was associated with significantly increased serum concentrations of GLUC (5.58 ± 2.07 versus 2.09 ± 0.83 ng/ml, p < 0.001) but not of EZ (0.92 ± 0.73 versus 0.55 ± 0.40 ng/ml, n.s.). Consequently, urinary excretion of GLUC was about threeâfold increased (9.96 ± 0.27 versus 3.10 ± 1.37 µg/day, p = 0.049) whereas renal clearance and the amount excreted via feces remained unchanged. Both EZ and GLUC were not overâproportionally distributed into investigated organs. Pâglycoprotein primary influences the oral absorption of ezetimibe in mice. Distribution, renal and fecal excretion of the drug seems not to be markedly affected by Pâglycoprotein. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96: 3478-3484, 2007
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 12, December 2007, Pages 3478-3484
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 12, December 2007, Pages 3478-3484
نویسندگان
Stefan Oswald, Christiane Koll, Werner Siegmund,