Effects and Pharmacokinetic Properties of the Rat/Human Corticotropin-Releasing Factor in Rhesus Monkeys

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Abstract
The biological effects and pharmacokinetic properties of the recently sequenced rat/human corticotropin-releasing factor (r/hCRF) were evaluated in the rhesus monkey and compared to those of the previously studied ovine corticotropin-releasing factor (oCRF). An i.v. bolus of 0, 0.1, 1, 10 and 100 .mu.g/kg r/hCRF and 1 .mu.g/kg of oCRF were given to rhesus monkeys (4-5 tests per dose). Serial blood samples were drawn before and up to 180 min after the injection for determination of plasma immunoreactive (IR) ACTH, cortisol and IR-r/hCR or IR-oCRF concentrations. Mean arterial blood pressure and heart rate were monitored. r/hCRF stimulated ACTH and cortisol secretion in a dose-dependent fashion. Its potency was similar to that of oCRF; however, r/hCRF, had a shorter half-life and a 3-fold higher MCR [metabolic clearance rate] than oCRF. A dose-dependent decrease in the MCR of r/hCRF was observed, which may indicate a saturation of the clearance mechanisms. Significant decreases in mean arterial blood pressure, increases in heart rate and a profound facial flush occurred at the dose of 100 .mu.g/kg r/hCRF. Apparently, r/hCRF stimulates ACTH and cortisol secretion in a nonhuman primate with a potency similar to that of oCRF. The peptide has marked hypotensive effects at high doses and is cleared 3 times more rapidly than oCRF.

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