種々高リン血症治療薬のリン酸吸着能に関する基礎的検討

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• Recently,hemodialysis patients have been steadily increasing and for such patients,it is very important to control serumphosphate levels in order to decrease cardiovascular risks.Currently,a variety of therapeutic drugs,such as calcium carbonate,lanthanum carbonate and sevelamer hydrochloride,are administered to hemodialysis patients to enhance phosphateclearance from the body.Several anion-exchange resins,among them colestimide and colestyramine,have also been consideredfor the treatment of hyperphosphatemia.However,the relative effectiveness of these drugs in interacting with phosphatehas not been examined.In the present study,we compared the phosphate-binding capacities of therapeutic agents for hyperphosphatemia using aconventional centrifugation method.After mixing drug suspensions and a phosphate solution together,the pH of the mixturewas adjusted to between 1.2 and 8.0.It was then gently shaken for 30 min and subjected to high-speed centrifugation.By determining the phosphate concentration in the resultant supernatant fluid by the molybdenum blue method,the amountsof phosphate bound to each drug were estimated.The phosphate-binding capacity in descending order was as follows :sevelamer hydrochloride (614 mg/g)>lanthanum carbonate (557 mg/g)>calcium carbonate (535 mg/g)>colestimide (256mg/g)>cholestyramine (98 mg/g)=colestipol (93 mg/g),indicating that sevelamer hydrochloride was most potent in bindingphosphate.However,the interaction between sevelamer hydrochloride and phosphate was pH-dependent,as it was forcalcium carbonate and colestimide,and became weaker as the medium pH increased.In contrast,lanthanum carbonate hydrateexhibited potent binding that was independent of pH.The present results therefore suggest that lanthanum carbonatewould be most effective therapeutic agent for inhibiting phosphate absorption in hemodialysis patients.

• 日本医療薬学会の論文

日本医療薬学会 | 論文

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