重组人甲状旁腺激素1-34多次皮下注射给药的人体药动学特征

Study on pharmacokinetics of recombinant human parathyroid hormone 1-34 after subcutaneous injection for multiple administration in healthy volunteers

目的研究健康志愿者多次皮下注射重组人甲状旁腺激素1-34[(rhPTH(1-34)]后体内的药动学特征。方法8名健康志愿者多次皮下注射rhPTH(1-34)后,采用放射免疫法测定血浆中rhPTH(1-34)浓度,评估它的药动学特性。结果rhPTH(1-34)的主要药动学参数如下:d 1,AUC0→t为(17103.3±2243.3)ng.min.L-1,AUC0→∞为(20471.3±2444.6)ng.min.L-1,ρmax为(171.2±34.2)ng.L-1,tmax为(38.1±15.1)min,t12为(55.7±3.9)min;d 7,AUC0→t为(17759.6±3781.5)ng.min.L-1,AUC0→∞为(20698.4±3374.6)ng.min.L-1,ρmax为(184.6±36.8)ng.L-1,tmax为(35.0±16.0)min,t12为(51.6±7.6)min,蓄积系数R为1.02±0.18。结论多次皮下注射rhPTH(1-34)后,与单次给药相比它在人体内的吸收、消除不随连续给药变化,药物在体内没有蓄积作用。rhPTH(1-34)的安全耐受性良好。性别对药动学参数没有影响。

AIM To study the pharmacokinetics of recombinant human parathyroid hormone 1-34 [rhPTH（1-34）] after subcutaneous injection for multiple administration in healthy volunteers. METHODS Eight healthy volunteers were selected to receive multiple doses of rhPTH（1-34）. The plasma concentrations were determined by radioimmunoassay. RESULTS The phannacokinetic parameters of rhPTH（1-34） were as follows： dl, AUC0→t was（17 103.3 ± 2 243.3）ng· min·L^-1,AUC0→∞ was（20 471.3 ±2 A.dd.6）ng·min·L^-1,ρmax was（171.2 ± 34.2）ng·L^-1, tmax was（38.1 ± 15.1） min, t1/2 was （55. 7 ± 3. 9） min; d 7, AUC0→t was （17 759. 6 ± 3 781. 5） ng·min· L^-1, AUC0→∞ was （20 698.4 ± 3 374.6） ng·min·L^-1, ρmax was （ 184.6 ± 36.8） ng·L^-1, tmax was （35.0 ± 16.0） min, t1/2 was （51.6± 7.6）min. The accumttlation coefficient （R） was （1.02±0.18）. CONCLUSION The absorption and elimination rates of rhPTH（1-34） are not changed after multiple administration of rhPTH（1-34） as compared with single dose. There is no accumulation of drug to be found in plasma, rhPTH（1-34） is well in tolerance and safety. Meanwhile gender has no effect on its pharmaeokinetics.