Pharmacokinetics of Synthetic Human Parathyroid Hormone 1-34 in man Measured by Cytochemical Bioassay and Radioimmunoassay

Abstract

1. Synthetic human parathyroid hormone (hPTH) 1-34 was given by intravenous injection to two healthy men. The time course of its appearance in and disappearance from the plasma was monitored both by cytochemical bioassay and by a specific radioimmunoassay (RIA) system. 2. Immunoreactive N-region parathyroid hormone (iPTH) reached peak concentrations in plasma at 2 min after injection, whereas peak concentrations of biologically active parathyroid hormone (bioPTH) were delayed until 4-6 min. Bioassayable PTH-like activity then disappeared from the plasma (mean transit times 5.8 and 8.6 min), approximately twice as fast as immuno-reactivity. 3. After separate subcutaneous administrations, a calculated 22-37% of administered hPTH 1-34 was subsequently detected in the plasma, by both assay systems. 4. It was not possible to explain fully the non-parallel appearances of bio- and immuno-reactivities in the plasma after intravenous injection nor the non-parallel disappearances after both intravenous and subcutaneous injections on the basis of the present data. It seems likely, however, that in the process of biological degradation the immunoreactive locus is inactivated by a different reaction from that which destroys bioactivity. 5. To investigate these activity dissociations further will require the application of microfractionation procedures in conjunction with both types of assay system.