title: Pharmacokinetics, tissue distribution and excretion of recombinant human parathyroid hormone 1-84 in animals.
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 (125)I-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 (125)I-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 (125)I-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 (125)I-rhPTH (1-84) in tissues/organs examined, appeared to be low in rats. The major elimination route was by urinary excretion.
authors: Department of Endocrinology, First Affiliated Hospital of the General Hospital of PLA, Beijing, 100048, China.
authors: Hua
authors: H
authors: Bai
authors: Danqing
authors: D
authors: Jing
authors: Hua
authors: H
authors: Jiang
authors: Shinan
authors: S
authors: Yin
mesh_terms: D000818:Animals; D005260:Female; D006207:Half-Life; D006801:Humans; D007118:Immunoassay; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007457:Iodine Radioisotopes / Q000737:chemistry; D008253:Macaca mulatta; D008297:Male; D010281:Parathyroid Hormone / Q000235:genetics / Q000378:metabolism / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics / Q000493:pharmacokinetics; D014018:Tissue Distribution; D014238:Trichloroacetic Acid / Q000737:chemistry
chemical_list: D007457:Iodine Radioisotopes; D010281:Parathyroid Hormone; D011994:Recombinant Proteins; D014238:Trichloroacetic Acid