Corticotropin-releasing factor: pharmacokinetics in man

Abstract

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 microgram/kg; n = 6) or as a continuous infusion (0.51 +/- 0.05 micrograms/kg X 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 X 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 X day). A small percentage of IR-CRF (approximately 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.