GROWTH HORMONE-RELEASING ACTIVITY OF HEXARELIN, A NEW SYNTHETIC HEXAPEPTIDE, AFTER INTRAVENOUS, SUBCUTANEOUS, INTRANASAL, AND ORAL-ADMINISTRATION IN MAN

We evaluated the GH-releasing activity of hexarelin, a new synthetic hexapeptide, after iv (1 and 2 mu g/kg), sc (1.5 and 3 mu g/kg), intranasal (20 mu g/kg), and oral (po; 20 and 40 mg) administration to 12 healthy young volunteers. Reference treatments were iv saline and GH-releasing hormone (GHRH; 1 mu g/kg). GH release (mean +/- SEM) after the iv dose of 1 mu g/kg hexarelin [area under the curve (AUC), 3175 +/- 506 mu g/min.L] was about 2 times higher than that induced by 1 mu g/kg GHRH (AUC, 1544 +/- 161 mu g/min.L; P < 0.001). Hexarelin (2 mu g/kg, iv) elicited a further increase in GH levels (AUC, 4422 +/- 626 mu g/min.L) compared to the 1 mu g/kg dose. The GH response to 2 mu g/kg hexarelin, iv, was very reproducible (AUC, 4016 +/- 563 vs. 3959 +/- 803 mu g/min.L). The sc administration of hexarelin produced a dose-dependent GH response (AUC, 3180 +/- 392 and 4459 +/- 566 mu g/min.L with 1.5 and 3 mu g/kg, respectively). Intranasal administration of 20 mu g/kg hexarelin induced GH release (AUC, 2642 +/- 452 mu g/min.L) similar to that caused by 1 mu g/kg, iv. Twenty and 40 mg hexarelin, po, produced a dose-related increase in GH levels (AUC, 2278 +/- 442 and 4079 +/- 514 mu g/min.L). Biological bioavailabilities were 77.0 +/- 10.5%, 4.8 +/- 0.9%, and 0.3 +/- 0.1% for the sc, intranasal, and po routes, respectively. This study shows that the GH response to hexarelin administered by the iv route has a limited variability and is superior to the response to GHRH. The GH-releasing activity appeared to be dose dependent. Thus, hexarelin could be clinically useful to stimulate GH secretion in humans.