کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10162106 | 1114316 | 2015 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Studies of Nontarget-Mediated Distribution of Human Full-Length IgG1 Antibody and Its FAb Fragment in Cardiovascular and Metabolic-Related Tissues
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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: Studies of Nontarget-Mediated Distribution of Human Full-Length IgG1 Antibody and Its FAb Fragment in Cardiovascular and Metabolic-Related Tissues Studies of Nontarget-Mediated Distribution of Human Full-Length IgG1 Antibody and Its FAb Fragment in Cardiovascular and Metabolic-Related Tissues](/preview/png/10162106.png)
چکیده انگلیسی
Tissue distribution and pharmacokinetics (PK) of full-length nontargeted antibody and its antigen-binding fragment (FAb) were evaluated for a range of tissues primarily of interest for cardiovascular and metabolic diseases. Mice were intravenously injected with a dose of 10Â mg/kg of either human IgGlor its FAb fragment; perfused tissues were collected at a range of time points over 3 weeks for the human IgG1 antibody and 1 week for the human FAb antibody. Tissues were homogenized and antibody concentrations were measured by specific immunoassays on the Gyros system. Exposure in terms of maximum concentration (Cmax) and area under the curve was assessed for all nine tissues. Tissue exposure of full-length antibody relative to plasma exposure was found to be between 1% and 10%, except for brain (0.2%). Relative concentrations of FAb antibody were the same, except for kidney tissue, where the antibody concentration was found to be ten times higher than in plasma. However, the absolute tissue uptake of full-length IgG was significantly higher than the absolute tissue uptake of the FAb antibody. This study provides a reference PK state for full-length whole and FAb antibodies in tissues related to cardiovascular and metabolic diseases that do not include antigen or antibody binding.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 5, May 2015, Pages 1825-1831
Journal: Journal of Pharmaceutical Sciences - Volume 104, Issue 5, May 2015, Pages 1825-1831
نویسندگان
Pia Davidsson, Ann-Sofi Söderling, Lena Svensson, Andrea Ahnmark, Christine Flodin, Ewa Wanag, Valentina Screpanti-Sundqvist, Peter Gennemark,