Pharmacokinetics of recombinant human parathyroid hormone after subcutaneous administration in Rhesus monkeys by immunoradiometric assay  

猕猴皮下注射重组人甲状旁腺激素的药代动力学研究(英文)

作　　者：宋雪伟[1] 陈知航[1] 车津晶[1] 单成启[1] 侯禹男[1] 郑仁玖 程远国[1] 

机构地区：[1]军事医学科学院微生物流行病研究所药物代谢动力学研究室,北京100071 [2]吉林省长白山科学研究院,吉林133613

出　　处：《Journal of Chinese Pharmaceutical Sciences》2008年第2期118-121,共4页中国药学（英文版）

摘　　要：The purpose of this research was to study the pharmacokinetics and the bioavailability of recombinant human parathyroid hormone [rhPTH （1-34）] in Rhesus monkeys after single and multiple subcutaneous administration. An immunoradiometric assay （IRMA） was used to determine the plasma drug concentration of rhFFH （1-34） after giving single dose of 10, 20 and 40 ug/kg and daily dose of 40 ug/kg for 7 d by subcutaneous administration, and intravenous injection of 20 ug/kg in Rhesus monkeys. The pharmacokinetic parameters were calculated by noncompartmental analysis. The drug plasma level quantitation range was from 0.027 to 2.22 ng/mL. The intra- and inter-assay precision （CV） of analysis were less than 15%, and the average recovery was about 93.0% ± 8.6% - 116.5% ± 14.0%. After subcutaneous administration of rhPTH（1-34） at dose of 10, 20 and 40 ug/kg, the average Tmax was 0.67, 0.5 and 0.83 h, Cmax were 1.85 ± 0.05, 3.23 ± 0.25 and 7.15 ± 1.19 ng/mL, the AUC（0-∞） were 3.4 ± 0.6, 10.7 ± 1.3 and 12.6 ± 1.5 ng/h/mL, and terminal-phase elimination T1/2 were 0.72 ± 0.10, 1.15 ± 0.10 and 1.03 ± 0.06 h, respectively. The absolute bioavailability of rhPTH （1-34） was 46.96% after subcutaneous administration of 20 ug/kg. There was no evidence of accumulation during systemic exposure of rhPTH （1-34） upon multiple dosing in Rhesus monkeys. The IRMA assay method provide reasonable sensitivity and specificity for the pharrnacokinetic study of rhPTH （1-34） after subcutaneous or intravenous administration in Rhesus monkeys. The pharmacokinetic characteristic of rhPTH （1-34） in monkeys shows linear relationship with the dose administered subcutaneously.研究猕猴皮下注射重组人甲状旁腺激素[rhPYH(1-34)]后的药代动力学及生物利用度。猕猴皮下注射rhPTH(1-34) 10,20和40μg/kg,静脉注射rhPYH(1-34)20μg/kg以及连续皮下注射rhPTH(1-34)40μg/kg(每天一次,连续14天),应用放免方法(IRMA)检测血浆样本中药物浓度,然后采用非房室模型计算药代动力学参数。IRMA方法检测血浆中rhPTH(1-34)的线性范围为0.027～2.22 ng/mL。日内和日间精密度都小于15%,并且平均回收率约为93.0%±8.6%～116.5%±14.0%。猕猴皮下注射rhPTH(1-34)10,20和40μg/kg后,平均达峰时间T_(max)分别为0.67,0.5和0.83 h,峰浓度C_(max)分别为1.85±0.05,3.23±0.25和7.15±1.19ng/mL,曲线下面积AUC_(0-∞)分别为3.4±0.6,10.7±1.3和12.6±1.5 ng/h/mL,末端相消除半衰期T_(1/2)分别为0.72±0.10,1.15±0.10和1.03±0.06h。猕猴皮下注射rhPTH(1-34)20μg/kg的绝对生物利用度为46.96%。连续注射猕猴rhPTH(1-34)后无药物蓄积。IRMA方法具有高灵敏度及专属性,适用于猕猴皮下注射rhPTH(1-34)后的药物药代动力学研究。在给予剂量范围内,猕猴体内的rhPTH(1-34)药物代谢符合线性动力学特征。

关 键 词：RhPTH （1-34） PHARMACOKINETIC IRMA BIOAVAILABILITY Rhesus monkey 

分 类 号：R96[医药卫生—药理学]