کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2484842 1114338 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Relationship Between the Urinary Excretion Mechanisms of Drugs and Their Physicochemical Properties
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Relationship Between the Urinary Excretion Mechanisms of Drugs and Their Physicochemical Properties
چکیده انگلیسی

ABSTRACTThe purpose of this study was to clarify the relationship between the physicochemical properties of drugs and their urinary excretion mechanisms. Three hundred twenty-five drugs were classified into the reabsorption, intermediate, and secretion types based on their ratio of renal clearance to protein-unbound fraction glomerular filtration rate. Fifty percent of ionized and neutral drugs were the secretion and reabsorption types, respectively. The mean molecular weight of the neutral drugs was slightly smaller than those of the ionized drugs (296 vs. 330–368 g/mol). The reabsorption-type anionic drugs were characterized by their low molecular weights (mean value 269 g/mol) and the logarithmic measure of the acid dissociation constants (pKa s) greater than 4.5, whereas the secretion-type anionic drugs all had pKas below 4.5. Cationic drugs with pKas lower than 8.0 tended to be the reabsorption type. Some cationic drugs were classified as the secretion type, despite their high molecular weights (734–811 g/mol) and high log P values (3.1–5.3). The organic anion transporter (OAT)1 and OAT3 substrates were all secretion-type drugs. The same trend was observed for the substrates of organic cation transporter 2, multidrug and toxin extrusion, multidrug resistance-associated protein 4, and multidrug resistance 1/breast cancer resistance protein, but substantial fractions of the substrates were categorized as the intermediate or reabsorption types (9%–38%). This work provides a clue to the renal elimination mechanism of new chemical entities during drug development.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 9, September 2013, Pages 3294–3301
نویسندگان
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