目的研究重组人甲状旁腺激素1-34(rhPTH1-34)对成骨细胞增殖及BMP-7、BMP-9基因表达的影响。方法通过不同剂量的重组人甲状旁腺素(rhPTH1-34)(0、10-11、10-10、10-9、10-8、10-7mol/L)间歇性(24 h/周期,前12 h rhPTH1-34干预)刺激体外...目的研究重组人甲状旁腺激素1-34(rhPTH1-34)对成骨细胞增殖及BMP-7、BMP-9基因表达的影响。方法通过不同剂量的重组人甲状旁腺素(rhPTH1-34)(0、10-11、10-10、10-9、10-8、10-7mol/L)间歇性(24 h/周期,前12 h rhPTH1-34干预)刺激体外培养的成骨细胞,用噻唑蓝(MTT)法检测细胞的增殖能力,RT-PCR法检测成骨细胞BMP-7、BMP-9基因的表达。结果间歇性小剂量rhPTH1-34可明显促进成骨细胞的增殖能力及增强BMP-7、BMP-9基因的表达。结论间歇性小剂量rhPTH1-34可促进成骨细胞增殖,可能与BMP-7、BMP-9基因表达相关。展开更多
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....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.展开更多
文摘目的研究重组人甲状旁腺激素1-34(rhPTH1-34)对成骨细胞增殖及BMP-7、BMP-9基因表达的影响。方法通过不同剂量的重组人甲状旁腺素(rhPTH1-34)(0、10-11、10-10、10-9、10-8、10-7mol/L)间歇性(24 h/周期,前12 h rhPTH1-34干预)刺激体外培养的成骨细胞,用噻唑蓝(MTT)法检测细胞的增殖能力,RT-PCR法检测成骨细胞BMP-7、BMP-9基因的表达。结果间歇性小剂量rhPTH1-34可明显促进成骨细胞的增殖能力及增强BMP-7、BMP-9基因的表达。结论间歇性小剂量rhPTH1-34可促进成骨细胞增殖,可能与BMP-7、BMP-9基因表达相关。
文摘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.
