Abboud Hanna, Coyne Daniel, Smolenski Olgierd, Anger Michael, Lunde Norman, Qiu Ping, Hippensteel Rich, Pradhan Rajendra S, Palaparthy Rameshraja V, Kavanaugh Anne, Melnick Joel Z, Williams Laura A, Batlle Daniel
University of Texas Health Science Center, San Antonio, Texas, USA.
Am J Nephrol. 2006;26(1):105-14. doi: 10.1159/000092033. Epub 2006 Mar 14.
Intermittent dosing of calcitriol for secondary hyperparathyroidism (SHPT) has been associated with greater parathyroid hormone (PTH) reduction with fewer calcemic and phosphatemic effects than daily (QD) dosing.
Secondary analyses of three randomized, double-blind, placebo-controlled multicenter studies in stage 3 and 4 chronic kidney disease (CKD) patients with SHPT were performed to compare three times per week (TIW) with QD dosing of paricalcitol. The pharmacokinetics of TIW and QD dosing of paricalcitol capsules were assessed in a separate group of healthy subjects.
Pharmacokinetics revealed similar steady state paricalcitol exposure between dosing regimens. In CKD patients, baseline data were similar between the TIW studies (n = 72, paricalcitol; n = 73, placebo) and QD studies (n = 35, paricalcitol; n = 40, placebo). Both dosing regimens resulted in similar efficacy (91%) for the primary end point of two consecutive > or = 30% decreases in intact PTH from baseline, but the QD regimen resulted in a greater percent reduction in intact PTH from baseline. The chances for developing increased serum calcium and phosphorus levels or Ca x P product were similar between paricalcitol and placebo groups for both treatment regimens. Furthermore, no difference in the risk for these elevations was detected between the TIW and QD regimens.
QD dosing of paricalcitol capsules is as efficacious as TIW dosing in achieving the primary end point (2 consecutive > or = 30% reductions in PTH) in stage 3 and 4 CKD patients with SHPT. Moreover, the QD regimen had no significant effect on hypercalcemia, hyperphosphatemia or Ca x P product as compared with placebo or intermittent dosing.
对于继发性甲状旁腺功能亢进症（SHPT），与每日（QD）给药相比，间歇性服用骨化三醇可使甲状旁腺激素（PTH）降低幅度更大，且血钙和血磷影响较小。
对三项针对3期和4期慢性肾脏病（CKD）合并SHPT患者的随机、双盲、安慰剂对照多中心研究进行二次分析，以比较帕立骨化醇每周三次（TIW）给药与QD给药的效果。在另一组健康受试者中评估了帕立骨化醇胶囊TIW和QD给药的药代动力学。
药代动力学显示，不同给药方案之间帕立骨化醇的稳态暴露相似。在CKD患者中，TIW研究（n = 72，帕立骨化醇；n = 73，安慰剂）和QD研究（n = 35，帕立骨化醇；n = 40，安慰剂）的基线数据相似。两种给药方案对于从基线开始连续两次完整PTH降低≥30%这一主要终点的疗效相似（91%），但QD方案使完整PTH从基线降低的百分比更大。两种治疗方案中，帕立骨化醇组和安慰剂组发生血清钙和磷水平升高或钙磷乘积升高的几率相似。此外，TIW和QD方案之间在这些升高风险方面未检测到差异。
对于3期和4期CKD合并SHPT患者，帕立骨化醇胶囊QD给药在达到主要终点（PTH连续两次降低≥30%）方面与TIW给药同样有效。此外，与安慰剂或间歇性给药相比，QD方案对高钙血症、高磷血症或钙磷乘积无显著影响。
