Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0847097 (acidity)
 15,165 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The patient-to-patient 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). Semi-automated computerized image analysis was then performed to measure swelling of the particles. We constructed a glass continuous-flow cell that allowed stationary particles and real-time 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.
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PMID:Transient acid exposure increases sevelamer HCl phosphate binding. 1750 13