Duggal Ajay, Hanus Martin, Zhorov Eugene, Dagher Rafif, Plone Melissa A, Goldberg Jeffrey, Burke Steven K
Genzyme Europe Research, Cambridge, England.
J Ren Nutr. 2006 Jul;16(3):248-52. doi: 10.1053/j.jrn.2006.04.006.
Sevelamer, a nonabsorbed, calcium- and metal-free dietary phosphate binder, consists of a polyallylamine polymer backbone with a cationic charge that shows a high capacity for binding anionically charged compounds such as phosphate. The currently licensed form of sevelamer, Renagel, exists as sevelamer hydrochloride, which disassociates in the acidic environment of the stomach and early gastrointestinal tract, exchanging the chloride ions attached to the polymer backbone for phosphate ions. The resulting absorption of these chloride ions has been reported to be accompanied by a reduction in serum levels of bicarbonate in some patients. To minimize the possibility of this effect, a new salt form of sevelamer has been developed in which carbonate replaces the chloride counter ion, thereby providing a source of buffer. The majority of phosphate binders exist only in tablet form and are dosed three times per day with meals. Genzyme has developed sevelamer carbonate in tablet form and also as a powder formulation that can be taken after mixing with water. This allows for an alternate and potentially more palatable way of dosing. Preliminary data exist suggesting that once daily dosing with sevelamer hydrochloride tablets provides similar phosphate control to three times daily dosing. By providing novel dosage forms and regimens for sevelamer-based phosphate binders, Genzyme will be providing patients and health care providers additional choices and flexibility in controlling phosphorus levels in chronic kidney disease. This should translate to increased compliance and improved rates of phosphate control.
司维拉姆是一种不被吸收的、不含钙和金属的膳食磷结合剂，由带有阳离子电荷的聚烯丙胺聚合物主链组成，该聚合物主链对诸如磷酸盐等带阴离子电荷的化合物具有高结合能力。司维拉姆目前获批的剂型Renagel是以盐酸司维拉姆的形式存在，它在胃和胃肠道早期的酸性环境中解离，聚合物主链上附着的氯离子与磷酸根离子交换。据报道，这些氯离子的吸收在一些患者中会伴有血清碳酸氢盐水平的降低。为了将这种影响的可能性降至最低，已开发出一种司维拉姆的新盐形式，其中碳酸根取代了氯离子抗衡离子，从而提供了一种缓冲源。大多数磷结合剂仅以片剂形式存在，每日随餐服用三次。健赞公司已开发出片剂形式的碳酸司维拉姆，也有粉末制剂，可与水混合后服用。这提供了一种替代的、可能更可口的给药方式。现有初步数据表明，盐酸司维拉姆片每日一次给药与每日三次给药对磷的控制效果相似。通过为基于司维拉姆的磷结合剂提供新颖的剂型和给药方案，健赞公司将为患者和医疗保健提供者在控制慢性肾病患者的磷水平方面提供更多选择和灵活性。这应该会转化为依从性的提高和磷控制率的改善。
