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The clearance and antidiuretic potency of neurohypophysial hormones in man, and their plasma binding and stability
Author(s) -
Fabian Miriam,
Forsling Mary L.,
Jones J. J.,
Pryor J. S.
Publication year - 1969
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1969.sp008937
Subject(s) - oxytocin , antidiuretic , vasopressin , endocrinology , medicine , hormone , chemistry , potency , volume of distribution , peptide hormone , pharmacokinetics , in vitro , biochemistry
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 μ‐u./ml.) In contrast, oxytocin was completely unbound. 7. Exogenous oxytocin was more stable than exogenous AVP in human plasma. At 4° C there was no significant loss of oxytocin until 7 days, whereas 20% of AVP was inactivated in 2 days. At 37° 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.