CAJ | 학술논문

研究猕猴皮下注射重组人甲状旁腺激素[rhPTH(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rhPTH(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Tmax分别为0.67,0.5和0.83 h,峰浓度Cmax分别为1.85±0.05,3.23±0.25和7.15±1.19 ng/mL.曲线下面积AUC0-∞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T1/2分别为0.72±0.10,1.15±0.10和1.03±0.06 h.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.
연구미후피하주사중조인갑상방선격소[rhPTH(1-34)]후적약대동역학급생물이용도.미후피하주사rhPTH(1-34)10,20화40μg/kg정맥주사rhPTH(1-34)20μg/kg이급련속피하주사rhPTH(1-34)40μg/kg(매천일차,련속14천),응용방면방법(IRMA)검측혈장양본중약물농도,연후채용비방실모형계산약대동역학삼수.IRMA방법검측혈장중rhPTH(1-34)적선성범위위0.027-2.22 ng/mL.일내화일간정밀도도소우15%,병차평균회수솔약위93.0%±8.6%～116.5%±14.0%.미후피하주사rhPTH(1-34)10,20화40μg/kg후,평균체봉시간Tmax분별위0.67,0.5화0.83 h,봉농도Cmax분별위1.85±0.05,3.23±0.25화7.15±1.19 ng/mL.곡선하면적AUC0-∞분별위3.4±0.6,10.7±1.3화12.6±1.5 ng/h/mL,말단상소제반쇠기T1/2분별위0.72±0.10,1.15±0.10화1.03±0.06 h.미후피하주사rhPTH(1-34)20μg/kg적절대생물이용도위46.96%.련속주사미후rhPTH(1-34)후무약물축적.IRMA방법구유고령민도급전속성,괄용우미후피하주사rhPTH(1-34)후적약물약대동역학연구.재급여제량범위내,미후체내적rhPTH(1-34)약물대사부합선성동역학특정.
The purpose of this research was to study the pharmacokinetics and the bioavailability of recombinant human parathy- roid 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 rhPTH (1-34) after giving single dose of 10, 20 and 40 μg/kg and daily dose of 40 μg/kg for 7 d by subcutaneous administration, and intravenous injection of 20 μg/kg in Rhesus monkeys. The pharmacokinetic parameters were calculated by noneompartmental 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 μg/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 subcutancous administration of 20 μg/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 pharmacokinetic 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.