BACKGROUND Approximately 30% of patients on dialysis received combination therapy for their phosphate binder prescription; however, few studies for combined effects of phosphate binders are reported. For the purpose of evaluating the efficacy of combination therapy, we compared the efficacy of sucroferric oxyhydroxide (PA21) combined with calcium carbonate with that of lanthanum carbonate hydrate, sevelamer hydrochloride, and ferric citrate hydrate combined with calcium carbonate. METHODS For in vitro studies, calcium carbonate and the other phosphate binders alone or in combination were stirred in phosphate solution at pH 2-8 for 2 h. After centrifuging the suspension, the phosphorus level in the supernatant was determined. For in vivo studies, rats were orally administered calcium carbonate and the other phosphate binders (except for sevelamer hydrochloride) alone or in combination, followed by oral administration of phosphate solution adjusted to pH 2 or 7. Serum samples were collected from the rats at predetermined timepoints and the serum phosphorus levels were determined and analyzed using a two-way analysis of variance. RESULTS In the in vitro study, the measured phosphate-binding capacity of combining sevelamer hydrochloride, PA21, and lanthanum carbonate hydrate with calcium carbonate was approximately equal to or greater than the theoretical values under most conditions. Furthermore, these combined effects were insensitive to pH in that order. The measured phosphate-binding capacity of ferric citrate hydrate combined with calcium carbonate was smaller than the theoretical values, and the combination did not exhibit efficacy under any of the tested conditions. In the in vivo study, the combined effect of PA21 and calcium carbonate at both pH values and that of lanthanum carbonate hydrate and calcium carbonate at pH 2 were additive. In contrast, the combined effect of lanthanum carbonate hydrate and calcium carbonate at pH 7 and that of ferric citrate hydrate and calcium carbonate at pH 2 were antagonistic. CONCLUSIONS These results suggest that coadministration of PA21 and calcium carbonate showed good and relatively stable efficacy throughout the range of the gastrointestinal pH and that combining lanthanum carbonate hydrate and ferric citrate hydrate with calcium carbonate may not produce the expected efficacy under certain conditions.

中文翻译：

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碳酸钙与羟基氧化亚铁和其他磷酸盐结合剂的联合作用之间的比较：体内和体外实验研究。

背景技术大约30％接受透析治疗的患者接受了磷酸盐结合剂处方的联合治疗。然而，很少有关于磷酸盐粘合剂的联合作用的研究报道。为了评估联合治疗的疗效，我们比较了羟基氧化硫铁氧铁（PA21）和碳酸钙与碳酸镧水合物，司维拉姆盐酸盐和柠檬酸铁水合物与碳酸钙的疗效。方法为了进行体外研究，将碳酸钙和其他磷酸盐粘合剂单独或组合在pH 2-8的磷酸盐溶液中搅拌2小时。离心悬浮液后，测定上清液中的磷水平。对于体内研究，单独或组合给大鼠口服碳酸钙和其他磷酸盐结合剂（盐酸司维拉姆除外），然后口服调节至pH 2或7的磷酸盐溶液。在预定的时间点从大鼠收集血清样品和血清磷使用双向方差分析确定并分析其水平。结果在体外研究中，在大多数条件下，将司维拉姆盐酸盐，PA21和碳酸镧水合物与碳酸钙结合使用时，测得的磷酸盐结合能力大约等于或大于理论值。此外，这些综合作用对该顺序的pH值不敏感。所测量的柠檬酸铁水合物与碳酸钙结合的磷酸盐结合能力小于理论值，并且该结合物在任何测试条件下均未显示出功效。在体内研究中，PA21和碳酸钙在pH值和水合碳酸镧和碳酸钙在pH 2时的联合作用是加和的。相反，在pH 7时水合碳酸镧和碳酸钙的结合作用与在pH 2时水合柠檬酸铁和碳酸钙的结合作用是拮抗的。