A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism
A calcimimetic agent lowers plasma parathyroid hormone levels in patients with secondary hyperparathyroidism
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DOI：
10.1046/j.1523-1755.2000.00183.x
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发表时间：
2000-07-01
影响因子：
19.6
通讯作者：
Coburn, JW
中科院分区：
文献类型：
--
作者：
Goodman, WG;Frazao, JM;Coburn, JW
背景。拟钙化剂R-568可降低血液透析患者轻度继发性甲状旁腺功能亢进患者血浆甲状旁腺激素（PTH）水平，但其对重度继发性甲状旁腺功能亢进患者的疗效尚未见研究。21例每周进行3次血液透析，血浆PTH水平在300 - 1200 pg/mL之间的患者被随机分配到15天的治疗中，使用100 mg R-568 （N = 16）或安慰剂（N = 5）。在口服给药后的第1、2、3、5、8、11、12和15天，每隔24小时测量血浆甲状旁腺激素和血离子钙水平。在给予R-568或安慰剂的受试者中，预处理PTH水平分别为599 +/- 105（平均+/- SE）和600 +/- 90 pg/mL，而在给予安慰剂的受试者中，治疗第一天的数值没有变化。相比之下，在初始剂量R-568后1小时、2小时和4小时，甲状旁腺激素水平分别下降66 +/- 5%、78 +/- 3%和70 +/- 3%，并在24小时内保持低于预处理值。第一次服用R-568后，血离子钙水平也有所下降，但在服用安慰剂的患者中没有变化。尽管在治疗的第二和第三天电离钙浓度较低，但在给予R-568的患者中，剂量前PTH水平分别为422 +/- 70和443 +/- 105 pg/mL，并且在给药后两小时每天下降50%以上。在R-568治疗的前9天，剂量前PTH水平逐渐下降，在研究期间仍低于预处理水平。服用R-568的患者血清总钙和血离子钙浓度较治疗前水平下降，而服用安慰剂的患者血清总钙和血离子钙浓度不变。16例接受R-568治疗的患者中，有7例血离子钙水平降至1.0 mmol/L以下；5名患者在出现低钙症状后退出研究，而3名患者在减少R-568剂量后完成了治疗。拟钙化剂R-568可迅速显著降低终末期肾病引起的继发性甲状旁腺功能亢进症患者血浆PTH水平。
Background. The calcimimetic agent R-568 lowers plasma parathyroid hormone (PTH) levels in hemodialysis patients with mild secondary hyperparathyroidism, but its efficacy in those with more severe secondary hyperparathyroidism has not been studied.Methods. Twenty-one patients undergoing hemodialysis three times per week with plasma PTH levels between 300 and 1200 pg/mL were randomly assigned to 15 days of treatment with either 100 mg of R-568 (N = 16) or placebo (N = 5). Plasma PTH and blood ionized calcium levels were measured at intervals of up to 24 hours after oral doses on days 1, 2, 3, 5, 8, 11, 12, and 15.Results. Pretreatment PTH levels were 599 +/- 105 (mean +/- SE) and 600 +/- 90 pg/mL in subjects given R-568 or placebo, respectively, and values on the first day of treatment did not change in those given placebo. In contrast, PTH levels fell by 66 +/- 5%, 78 +/- 3%, and 70 +/- 3% at one, two, and four hours, respectively, after initial doses of R-568, remaining below pretreatment values for 24 hours. Blood ionized calcium levels also decreased after the first dose of R-568 but did not change in patients given placebo. Despite lower ionized calcium concentrations on both the second and third days of treatment, predose PTH levels were 422 +/- 70 and 443 +/- 105 pg/mL, respectively, in patients given R-568, and values fell each day by more than 50% two hours after drug administration. Predose PTH levels declined progressively over the first nine days of treatment with R-568 and remained below pretreatment levels for the duration of study. Serum total and blood ionized calcium concentrations decreased from pretreatment levels in patients given R-568, whereas values were unchanged in those given placebo. Blood ionized calcium levels fell below 1.0 mmol/L in 7 of 16 patients receiving R-568; five patients withdrew from study after developing symptoms of hypocalcemia, whereas three completed treatment after the dose of R-568 was reduced.Conclusions. The calcimimetic R-568 rapidly and markedly lowers plasma PTH levels in patients with secondary hyperparathyroidism caused by end-stage renal disease.