重组人甲状旁腺激素在中国健康人体内的药动学

Pharmacokinetics study of recombinant human parathyroid hormone in Chinese healthy volunteers

目的:观察治疗骨质疏松新药重组人甲状旁腺激素[rh-PTH(1-84)]对人体的安全性,耐受性并进行药动学考察。方法:单次皮下注射rh-PTH(1-84)1,2,4μg·kg-1,给药后0～24h采集血清样本,使用酶联免疫疗法测定血清中rh-PTH(1-84)的浓度。结果:rh-PTH(1-84)代谢符合非房室模型,在健康人体内表现为线性药动学特征,平均Cmax和AUC0-t范围分别从543.47～1845ng·L-1和2358.6～9232.12ng·L-1·h,平均消除半衰期分别为1.85,1.79,2.57h。结论:rh-PTH(1-84)不良反应轻微,人体可耐受,推荐Ⅱ期临床用药剂量为每天给药100μg。若体质量差别较大时,按照每60kg体质量100μg药物计算。

OBJECTIVE To determine the safety, tolerability and pharmacokinetics parameters of a new drug recombinant human parathyroid hormone [rhPTH（1-84）] for treatment of osteoporosis. METHODS The pharmacokinetic of rhPTH（1- 84） was studied. The subcutaneous injection dose of 1,2 and 4 μg·kg^-1 , respectively. Serum sample were obtained before ad- ministration and up to 24 hours after the administration. The concentration of rhPTH was determined by ELISA assay. RESULTS The disposition of rhPTH（1-84） was fitted well with a non-compartment pharmacokinetic model and rhPTH（1-84） had the characteristics of liner pharrnacokinetics. The mean Cmax and AUC0-24 ranging from approximately 543.47 to 1 845 ng·L^-1and2358.6to9232.12ng·L^-1·h. Themean t1/2βwas1. 85,1. 79 and 2. 57 h. CONCLUSlON The side effect of rhPTH （1-84） is mild and well tolerant. We recommend that the dose for Phase Ⅱ clinical trial should be 100 μg every day as singular agent. When the difference of weight is significant, the optimal dose of administration is calculated according of 100 μg per 60 kg.