کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2486999 1114399 2009 15 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Sulphonylurea physicochemical-pharmacokinetic relationships in the pancreas and liver
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
پیش نمایش صفحه اول مقاله
Sulphonylurea physicochemical-pharmacokinetic relationships in the pancreas and liver
چکیده انگلیسی
This study examined the physicochemical-pharmacokinetic relationships for the sulphonylureas in the perfused rat pancreas and liver. Multiple indicator dilution studies were conducted with bolus injections of tolbutamide, chlorpropamide, gliclazide, glipizide, glibenclamide and glimepiride, and a reference marker albumin, in the perfused pancreas and liver. Individual solute pharmacokinetics were analysed using nonparametric moment analysis and nonlinear regression assuming a physiologically based pharmacokinetic model. All solutes had similar shaped outflow concentration-time profiles in both the pancreas and liver, but varied in extraction. Negligible drug extraction was evident in the pancreas. Hepatic extraction ranged from 0.03 (tolbutamide) to 0.52 (glibenclamide) and could be related to solute lipophilicity and perfusate protein binding. The sulphonylurea mean transit times in both the pancreas and liver varied four- and ninefold respectively and were related to the lipophilicity and perfusate protein binding of the drug. The permeability surface area product of sulphonylureas from the perfusate into the organs were greater in the liver and were mainly determined by lipophilicity (pancreas, r2 = 0.89; liver, r2 = 0.80). The distribution of the sulphonylureas in both the perfused pancreas and perfused liver was dependent on their lipophilicity and perfusate protein binding. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:2807-2821, 2009
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 98, Issue 8, August 2009, Pages 2807-2821
نویسندگان
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