An homologous and sensitive radioimmunoassay for the synthetic amino-terminal (1-34) fragment of human parathyroid hormone: application to the clearance of this peptide administered in vivo.
The synthetic 1-34 amino-terminal fragment of human parathyroid hormone (hPTH 1-34) is undergoing multicentre clinical trials to assess its long term therapeutic potential in the treatment of osteoporosis. An homologous radioimmunoassay (reagents prepared from the synthetic hPTH 1-34 peptide) has been developed to monitor the pharmacokinetics of hPTH 1-34 in man and in a dog model. The assay is rugged, sensitive (detection limit 1.75 x 10(-11) moles/litre) and precise (coefficient of variation 6%). Three different ampouled preparations of the native intact hPTH 1-84, of different degrees of purity (approximately 3%-90% pure) gave complete log dose response curves parallel to that of the ampouled synthetic hPTH 1-34 peptide, and were equipotent on a molar basis. Native intact bovine PTH 1-84 showed an incomplete non-parallel displacement curve; there was no recognition of synthetic hPTH 44-68 and 53-84 peptides. Preliminary application of the assay to the determination of the plasma disappearance of hPTH 1-34 in man and dog gave half-times (t1/2) of 3-8 minutes for a first exponential component and 12-18 minutes for the second; in the dog, metabolic clearance rate was calculated to be 9ml/kg/minute and the distribution space 160ml/kg.
D000596:Amino Acids / Q000276:immunology*; D000818:Animals; D004285:Dogs; D004306:Dose-Response Relationship, Immunologic; D006801:Humans; D007106:Immune Sera / Q000494:pharmacology; D008024:Ligands; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood / Q000276:immunology* / Q000302:isolation & purification; D010455:Peptides / Q000008:administration & dosage* / Q000378:metabolism; D011863:Radioimmunoassay
D000596:Amino Acids; D007106:Immune Sera; D008024:Ligands; D010281:Parathyroid Hormone; D010455:Peptides