RESUMO
The occurrence of hPTH-1-37 as the native bioactive circulating form of PTH-1-84 has now been obtained using a specific purification procedure for circulating parathyroid hormone, which involves a newly developed immunoenzymetric assay for N-terminally intact hPTH. In combination with two different methods of mass spectrometry, the molecular weight of the isolated immunoreactive peptide was shown to be 4401 Da, which corresponds to hPTH-1-37. Synthetic hPTH-1-37 material was tested in the chick bioassay and produced a clearcut increase in serum calcium concentration. We conclude that hPTH-1-37 is the native bioactive fragment of hPTH-1-84 in circulation.
Assuntos
Hormônio Paratireóideo/química , Fragmentos de Peptídeos/química , Animais , Galinhas , Humanos , Hormônio Paratireóideo/sangue , Hormônio Paratireóideo/isolamento & purificação , Hormônio Paratireóideo/metabolismo , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/isolamento & purificação , Fragmentos de Peptídeos/metabolismoRESUMO
The total body clearance of recombinant human erythropoietin (rhEPO) calculated per kilogram of body weight increased in the order man = dog < rat << mouse. The differences disappeared or were reversed when clearance was expressed per square meter of body surface. There was no similar species difference in terminal half life. Total body clearance increased with the dose in dogs and mice, but not in rats. The bioavailability from a subcutaneous depot was 80% in dogs, 76% in rats, and 70% in mice. The absorption from the subcutaneous depot is rapid in rats and mice, but slow in dogs. The pharmacodynamic activity of rhEPO injected by both routes was compared in polycythemic mice. The equipotent doses were 2.44 times higher with intravenous than with subcutaneous injection. Taking into account the bioavailability of 70% from a subcutaneous depot, one obtains a potency ratio of 3.5 for absorbed subcutaneous versus intravenous rhEPO.