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

Abstract

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 radioimunoassay (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 ± 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.