关键词: 重组人甲状旁腺激素, 重组人甲状旁腺激素, 重组人甲状旁腺激素, 药代动力学, 药代动力学, 药代动力学, IRMA, IRMA, IRMA, 生物利用度, 生物利用度, 生物利用度, 猕猴, 猕猴, 猕猴, , ,

Abstract:

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 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 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 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 subcutaneous 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.

Key words: RhPTH (1-34), RhPTH (1-34), Pharmacokinetic, Pharmacokinetic, IRMA, IRMA, Bioavailability, Bioavailability, Rhesus monkey, Rhesus monkey, ,