The clearance and antidiuretic potency of neurohypophysial hormones in man, and their plasma binding and stability.

1. Bio-assay techniques have been used to measure plasma levels of neurohypophysial hormones in man, following either a single injection or a continuous infusion.2. The median half-life of oxytocin after a single injection of 2 u. was 3.2 min (2.0-5.7, 95% confidence limits); this increased significantly (P < 0.01) to 4.8 min (4.4-6.1) when the hormone was infused at a rate of 500 m-u./min. The vasopressins had appreciably longer half-lives. After a single injection of 1 or 1.5 u. 8-lysine vasopressin (LVP), the half-life was 5.7 min (3.6-6.0). Continuous infusions of the hormones at a rate of 120 m-u./min yielded half-lives of 5.5 min (5.0-7.1) for LVP, and 5.6 min (3.9-9.5) for 8-arginine vasopressin (AVP).3. The apparent volumes of distribution of the hormones were all of the order of two thirds the extracellular volume.4. In accordance with its shorter half-life, the clearance of oxytocin was greater than that of the vasopressins (1.5 l./min, compared with 1.0 l./min).5. The antidiuretic potencies of the hormones were studied in over-hydrated subjects, by measuring the rate of urine excretion following an I.V. injection. Duration of antidiuretic action increased in the order: oxytocin, LVP, AVP. A 5:1 mixture of oxytocin and AVP was not as long-lasting as AVP alone. 8.5% (4-22) of an administered dose of AVP was excreted in the urine, and this amount was significantly correlated with urine volume (r = +0.67, P < 0.05).6. Ultrafiltration of human plasma containing exogenous hormones showed that 30% (13-50) of AVP was bound, the degree of binding being independent of concentration over the range used (50-400 mu-u./ml.) In contrast, oxytocin was completely unbound.7. Exogenous oxytocin was more stable than exogenous AVP in human plasma. At 4 degrees C there was no significant loss of oxytocin until 7 days, whereas 20% of AVP was inactivated in 2 days. At 37 degrees C a 20% loss of AVP occurred within 4 hr, and a 50% loss within 24 hr; corresponding times for oxytocin were 24 and 48 hr.