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| 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 |
| 投稿时间：2013-02-02 |
| DOI： |
| 中文关键词: 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 |
| 英文关键词:Recombinant human parathyroid hormones rhPTH (1-84) for injection Ovariectomized osteoporosis rats Pharmacokinetics Radioimmunoassay |
| 基金项目:康缘中医药科技创新基金（HZ1009KY）；江苏省中医药领军人才（LJ2009002） |
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| 中文摘要: |
| 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。 |
| 英文摘要: |
| 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 ovariectomy was performed), and each group had 8 rats.At the 4th week after the surgery, rats received a subcutaneous injection of 1μg/kg, 2μg/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 . |
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