کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486123 | 1114375 | 2007 | 9 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Decreased Drug Penetration in Inflamed Tissue Related to Changed Mucosal Metabolism in Experimental Colitis
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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
Pathophysiologic changes in mucosal protein expression inflammatory bowel disease (IBD) may affect drug concentration in mucosal tissue making it highly relevant to drug dose at the site of action and subsequently for success of the therapy. Tissue samples from an experimental colitis rat model were mounted in Ussing chambers and intratissue concentrations of diverse compounds were quantified. Studies with healthy versus colitis tissue samples and respective microsomal fractions made it possible to assess the involvement of Pâglycoprotein (Pâgp) and cytochrome P450 3A (CYP3A) on tissue penetration behavior. Pâgpârelated efflux was slightly increased for colitis tissue. Metabolism studies exhibited higher tacrolimus and testosterone mucosal metabolism in inflamed tissue. However, similar metabolic activity was observed for healthy and colitis groups with equivalent CYP3A expression levels in respective microsome fractions. Severity of colitis as determined by myeloperoxidase activity was found to have linear correlation to changes in tacrolimus degradation (R2 = 0.8299). It is hypothesized that increased drug metabolism is dependent on the number of cells infiltrating inflamed tissue. A dominant contribution of immuneârelated cells to observed variations in mucosal drug metabolism has been determined. This observed pathophysiologic mechanism may have a significant influence on available drug concentrations at the inflammation site, thus modifying antiâinflammatory efficiency of the therapy. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96:2145-2153, 2007
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 8, August 2007, Pages 2145-2153
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 8, August 2007, Pages 2145-2153
نویسندگان
Yann Pellequer, Verena Weissenborn, Alf Lamprecht,