Pieper Anne-Kathrin, Buhle Franziska, Bauer Steffen, Mai Ingrid, Budde Klemens, Haffner Dieter, Neumayer Hans-Hellmut, Querfeld Uwe
Department of Pediatric Nephrology, Charité, Humboldt University, Berlin, Germany.
Nephrol Dial Transplant. 2004 Oct;19(10):2630-3. doi: 10.1093/ndt/gfh446. Epub 2004 Aug 10.
After renal transplantation, patients with insufficient graft function may require phosphate binders. It is still unknown if sevelamer, a new calcium-free phosphate binder, interferes with the uptake of immunosuppressants. We studied its effects on the pharmacokinetics of cyclosporin A (CsA) and mycophenolate mofetil.
We examined 10 adults and eight children with stable renal graft function and stable CsA trough levels. A 12 h pharmacokinetic profile (10 observation points) was conducted without sevelamer, after a single dose and after 4 days of treatment with it. CsA levels were measured with both a monoclonal antibody assay (CEDIA) and a polyclonal antibody assay (FPIA), mycophenolic acid (MPA) levels by EMIT assay and CsA metabolites AM1, AM9 and AM4N by a modified HPLC method.
Sevelamer had no significant effect on CsA kinetics [area under the curve (AUC), peak concentration (C(max)), time of C(max)]. The AUC of AM1 was decreased by 30% and C(max) by 25% after 4 days of sevelamer intake. MPA levels were significantly reduced by a mean of 25% of the AUC (P<0.05) and by 30% of the C(max) after a single dose of sevelamer.
A single sevelamer dose reduces the C(max) and the AUC of MPA. Its intake for several days does not significantly influence CsA kinetics.
肾移植后，移植肾功能不全的患者可能需要使用磷结合剂。新型无钙磷结合剂碳酸司维拉姆是否会干扰免疫抑制剂的吸收尚不清楚。我们研究了其对环孢素A（CsA）和霉酚酸酯药代动力学的影响。
我们检查了10名成年和8名儿童肾移植功能稳定且CsA谷浓度稳定的患者。在未服用碳酸司维拉姆时、单剂量服用后以及服用4天后进行了12小时的药代动力学分析（10个观察点）。使用单克隆抗体测定法（CEDIA）和多克隆抗体测定法（FPIA）测量CsA水平，通过酶放大免疫测定法测量霉酚酸（MPA）水平，并通过改良的高效液相色谱法测量CsA代谢物AM1、AM9和AM4N。
碳酸司维拉姆对CsA的动力学[曲线下面积（AUC）、峰浓度（C(max)）、C(max)出现时间]无显著影响。服用碳酸司维拉姆4天后，AM1的AUC降低了30%，C(max)降低了25%。单剂量服用碳酸司维拉姆后，MPA水平的AUC平均显著降低25%（P<0.05），C(max)降低30%。
单次服用碳酸司维拉姆可降低MPA的C(max)和AUC。连续服用数天对CsA的动力学无显著影响。
