کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
10162721 1114349 2013 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
In Vitro Protein Binding of Liraglutide in Human Plasma Determined by Reiterated Stepwise Equilibrium Dialysis
ترجمه فارسی عنوان
پیوند پروتئین در پروتئین لیگرگلوتید در پلاسمای انسانی تعیین شده توسط دیالیز تعادل متوالی گام به گام
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی اکتشاف دارویی
چکیده انگلیسی
Liraglutide is a human glucagon-like peptide-1 (GLP-1) analogue approved for the treatment of type 2 diabetes. It is based on human GLP-1 with the addition of a 16-carbon fatty acid, which facilitates binding to plasma proteins, thus prolonging the elimination half-life and allowing once-daily administration. It has not been possible to quantify liraglutide protein binding by ultrafiltration (the usual method of choice), as the lipophilic molecule becomes trapped in the filter membrane. Therefore, the aim of this study was to develop a methodology that could determine the extent of liraglutide binding to plasma proteins in vitro. We report here the details of a novel reiterated stepwise equilibrium dialysis assay that has successfully been used to quantify liraglutide plasma protein binding. The assay allowed quantification of liraglutide binding to proteins in purified plasma protein solutions and human plasma samples and was effective at plasma dilutions as low as 5%. At a clinically relevant liraglutide concentration (104 pM), greater than 98.9% of liraglutide was bound to protein. Specific binding to human serum albumin and α1-acid glycoprotein was 99.4% and 99.3%, respectively. The novel methodology described herein could have an application in the quantification of plasma protein binding of other highly lipophilic drug molecules. © 2013 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 102:2882-2888, 2013
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 102, Issue 8, August 2013, Pages 2882-2888
نویسندگان
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