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Corticotropin-Releasing Factor: Pharmacokinetics in Man

Developmental Endocrinology Branch, National Institute of Child Health and Human Development, Surgical Neurology Branch, National Institute of Neurological and Communicative Diseases and Stroke Bethesda, Maryland 20205
Biological Psychiatry Branch, National Institute of Mental Health, National Institutes of Health Bethesda, Maryland 20205

Address requests for reprints to: George P. Chrousos, M.D., Building 10, Room 10B09, Bethesda, Maryland 20205.

Corticotropin-releasing factor (CRF)a 41-amino acid peptide isolated and sequenced from ovine hypothalami, has potential clinical application as a provocative test of the hypothalamic-pituitary-adrenal axis. To define its pharmacokinetic parameters in man, we measured the MCR and plasma half-life of immunoreactive CRF (IR-CRF) by the pulse injection and continuous infusion methods. Synthetic ovine CRF was given to 12 normal men as a bolus injection (1 µg/kg; n = 6) or as a continuous infusion (0.51 ± 0.05 µg/kg-h; n = 6) over 8 h. The disappearance curve of IR-CRF from plasma was biexponential. The plasma half-life of IR-CRF was 11.6 ± 1.5 min (mean ± SE) for the fast component and 73 ± 8 min for the slow component. The MCR using the pulse injection technique was 95 ± 11 liters/m² -day, and the volume of distribution was 6.2 ± 0.5 liters. Continuous infusion of CRF gave approximately the same MCR (88 ± 7 liters/m² day). A small percentage of IR-CRF (0.03%) was found in the urine at the end of the continuous infusion. The relatively low MCR of CRF may explain its prolonged biological action in primates and man.

^* Supported by Deutsche Forschungsgemeinschaft Grant SCHU 506, 1-2.

Received May 2, 1983.

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