骨质疏松症大鼠注射重组人甲状旁腺素药动学研究  

Pharmacokinetic study of the injection of recombinant human parathyroid hormone(1-84) in osteoporotic rats

作　　者：王胜军 杨澔侠 张晶[2] 姚昶[3] 

机构地区：[1]无锡市第九人民医院,江苏无锡214063 [2]南京中医药大学,南京210005 [3]江苏省中医院,南京210029

出　　处：《中国骨质疏松杂志》2013年第12期1232-1236,共5页Chinese Journal of Osteoporosis

基　　金：康缘中医药科技创新基金(HZ1009KY);江苏省中医药领军人才(LJ2009002)

摘　　要：目的研究注射用重组人甲状旁腺素rhPTH(1-84)在去卵巢骨质疏松症大鼠的药代动力学特征。方法 48只大鼠(250±10)g,分成对照组(切除卵巢周围小块脂肪组织)和模型组(双侧卵巢切除),每组8只,手术4周后皮下注射1.0、2.0、4.0 ug/kg rhPTH(1-84),采用放射免疫分析法测定rhPTH(1-84)不同时间点的血药浓度,计算药代动力学参数。结果 rhPTH(1-84)在24～1850 pg/mL范围内线性关系良好,最低检测量为10 pg/mL;血浆提取回收率80.2%～90.6%;模型组低、中、高三个剂量的药动力学参数AUC(0-∞)分别为(24628.9±1281)、(47059.3±3311)和(96652.1±2174)ng/(L·min);对照组AUC(0-∞)分别为(21974.0±1587)、(42651.2±1336)和(87736.8±1938)ng/(L·min)。结论单次皮下注射rhPTH(1-84)在低、中、高3个剂量内,Cmax、AUC(0-∞)在2组动物中均呈线性代谢特征,模型组双峰特征明显,可以为设计和优化临床研究及给药方案提供重要信息。Objective To study the pharmacokinetic characteristics of injected recombinant human parathyroid hormone rhPTH （1-84） in ovariectomized rats with osteoporosis. Methods Forty-eight rats, with an average weight of 250 ± 10g, were randomly divided into control group （small piece of adipose tissue around the ovary was removed） and model group （bilateral ovarieetomy was performed） , and each group had 8 rats. At the 4th week after the surgery, rats received a subcutaneous injection of 1 μg/kg, 2 μg/kg, or 4 μg/kg rhPTH （1-84） , respectively. The plasma concentration of rhPTH （1-84） at different time points was determined using radioimmunoassay method. The pharmacokinetic parameters were calculated. Results Excellent linear correlation was showed within the range of 24-1850 pg/mL. The minimum detection of rhPTH （1-84） in plasma was 10 pg/mL. The extraction efficiency in plasma was within the range of 80.2-90.6%. The AUC （0-∞）, a pharmacokinetic parameter, in low, middle, and high dose model group was 24628.9 ± 1281, 47059.3 ± 3311, and 96652.1 ± 2174 ng/L. min, respectively. The AUC （0-∞） in control group was 21974.0 ± 1587, 42651.2 ± 1336, and 87736.8 ± 1938 ng/L.min, respectively. Conclusion After the single injection of low, middle, and high dose of rhPTH（1-84） , the Cmax and ACU （0-∞） in both groups show a linear metabolic characteristics. The plasma concentration time curves show a clear bimodal in model groups, which can provide important information for the drug design and optimization of clinical research.

关 键 词：注射用重组人甲状旁腺素rhPTH(1—84) 去卵巢骨质疏松症大鼠 药代动力学 放射免疫分析法 

分 类 号：R965.2[医药卫生—药理学]