口服降钙素治疗骨质疏松的最佳药物递送和疗效的骨吸收日变化研究。

M A Karsdal, I Byrjalsen, B J Riis, C Christiansen
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引用次数: 47

摘要

背景:骨吸收表现出明显的日变化。当骨吸收达到峰值时,可逆的骨吸收抑制可能会产生最好的效果。该研究的目的是评估0.8 mg口服鲑鱼降钙素(sCT)的药代动力学(PK)和药效学(PD)特征以及药物摄入时间的影响。方法:该研究是一项随机、双盲、双虚拟、安慰剂对照的I期研究,旨在评估0.8 mg口服sCT在健康绝经后妇女中的药代动力学(PK)和药效学(PD)特征。共纳入81名受试者,目的是调查早上8:00给药(n = 42)、17:00餐前给药(n = 20)和22:00晚上给药(n = 19)。评估血浆sCT浓度和骨吸收(I型胶原c -末端末端肽(CTX-I))。结果:早上和晚餐前给药导致sCT浓度相当,为45 pg/ml,而晚上给药有降低Cmax的趋势,平均为24 pg/ml。与安慰剂的最大差异出现在给药后1 - 3小时,早晨给药抑制40 - 50%,晚餐前和晚上给药抑制约75%,这是由于昼夜节律变化导致骨吸收增加。结论:口服鲑鱼降钙素0.8 mg可有效抑制血清CTX,与给药时间无关。餐前剂量导致最佳疗效反应,对应于骨吸收的总体抑制25%。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin.

Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin.

Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin.

Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin.

Background: Bone resorption displays marked diurnal variation. Reversible inhibition of bone resorption may result in best possible efficacy when bone resorption peaks. The aim of the study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral salmon calcitonin (sCT) and the effect of timing of drug intake.

Methods: The study was a randomized, double-blind, double-dummy, placebo-controlled, phase I study to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral sCT in healthy postmenopausal women. Totally 81 subjects were included, aimed at investigation of a morning dose given at 8:00 (n = 42), a pre-dinner dose given at 17:00 (n = 20), and an evening dose given at 22:00 (n = 19). Plasma sCT concentrations and bone resorption (C-terminal-telopeptide of collagen type I (CTX-I)) was assessed.

Results: Morning and pre-dinner dosing led to comparable concentration of sCT of 45 pg/ml, whereas there was a tendency towards lower Cmax for the evening dosing having a mean of 24 pg/ml. The maximum difference from placebo was observed 1 to 3 hours post-dose with a 40 to 50% suppression consequent to morning dose, and about 75% suppression after pre-dinner and evening dose, due to the increase bone resorption as a result of circadian variation.

Conclusion: The study suggests that orally administered 0.8 mg of salmon calcitonin was effective in suppression of serum CTX irrespective of time of dosing. The pre-dinner dosing resulted in optimum efficacy response corresponding to an overall suppression of bone resorption by 25%.

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