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Pharmacokinetics, Tissue Distribution and Excretion of Recombinant Human Parathyroid Hormone 1–84 in Animals

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Abstract

To study the plasma pharmacokinetics and accumulation of the recombinant human parathyroid hormone (rhPTH) (1–84) in rhesus monkeys, and the tissue distribution and excretion profiles of 125I-rhPTH (1–84) in rats. The concentration of rhPTH (1–84) in plasma samples were determined by an enzyme immunoassay (EIA) method after subcutaneous and intravenous bolus injection. The tissue distribution and urinary, fecal and biliary excretion patterns of 125I-rhPTH (1–84) were investigated by trichloroacetic acid (TCA) precipitation method. Following subcutaneous (sc) administration rhPTH (1–84) in rhesus monkeys, rhPTH (1–84) exhibited rapid absorption and elimination and had no accumulated tendency after successive sc administration. Following sc administration 125I-rhPTH (1–84) in rats, the TCA-precipitated radioactivity was widely distributed and rapidly diminished in most tissues. Approximately 83.9 and 6.8 % of the total radioactivity was recovered in urine and feces by 72 h postdosing, respectively; whereas 4.1 % excreted into bile up to 24 h postdosing. The pharmacokinetics of rhPTH (1–84) complied with linear kinetics within the examined dose range following a single sc administration had no accumulated tendency following multiple sc administration in rhesus monkeys. The accumulation of 125I-rhPTH (1–84) in tissues/organs examined, appeared to be low in rats. The major elimination route was by urinary excretion.

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Correspondence to Shinan Yin.

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Bai, H., Jing, D., Jiang, H. et al. Pharmacokinetics, Tissue Distribution and Excretion of Recombinant Human Parathyroid Hormone 1–84 in Animals. Cell Biochem Biophys 66, 379–387 (2013). https://doi.org/10.1007/s12013-012-9477-4

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