کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2486124 | 1114375 | 2007 | 7 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Transient acid exposure increases sevelamer HCl phosphate binding*
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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
The patientâtoâpatient variability in the dosing of sevelamer HCl for phosphate control led us to test whether the binder's transient exposure to acidic environments (such as the stomach) might alter the compound so as to change its subsequent binding capacity in the more alkaline small intestine. We hypothesized that an acid milieu could either increase the reactive sites (protonated amine groups) or make the polymer more hydrophilic (hydration and swelling allowing more phosphate to reach those sites). Eight hundred milligrams of Renagel® tablets were exposed to pHs 1, 2.3, and 7 (n = 7 each acidity level) for 1 h. NaCl was added to keep ionic strength the same. Measured by atomic emission phosphate uptake after 3 h at pH 7 was, respectively, 3.13 ± 0.21, 2.72 ± 0.35, and 1.85 ± 0.46 mequiv./g (p = 0.0006, pH 1 vs. pH 7). Semiâautomated computerized image analysis was then performed to measure swelling of the particles. We constructed a glass continuousâflow cell that allowed stationary particles and realâtime photography. Using digitized optical measurements there was no difference (p > 0.8) between the swelling after 1 h of pH 1 or 7 solutions (60.2 ± 14.8% vs. 59.5 ± 9.8% increase in diameter). Our findings support the importance of transient acid exposure in enhancing phosphate binding, due to increased protonated sites rather than by more swelling. Patients with acquired or pharmacologic achlorhydria would not benefit from this unexpected in vivo reaction. Possibly manufacturing sevelamer with a higher degree of protonation or administering it with appropriately acidic vehicles or beverages remains to be investigated. © 2007 WileyâLiss, Inc. and the American Pharmacists Association J Pharm Sci 96:2154-2160, 2007
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 8, August 2007, Pages 2154-2160
Journal: Journal of Pharmaceutical Sciences - Volume 96, Issue 8, August 2007, Pages 2154-2160
نویسندگان
Edward A. Ross, William E. III, Anika A. Odukale, Nicolas A. Alba, Christopher D. Batich,