title: Growth hormone-releasing activity of hexarelin, a new synthetic hexapeptide, after intravenous, subcutaneous, intranasal, and oral administration in man.
abstract: We evaluated the GH-releasing activity of hexarelin, a new synthetic hexapeptide, after i.v. (1 and 2 micrograms/kg), sc (1.5 and 3 micrograms/kg), intranasal (20 micrograms/kg), and oral (po; 20 and 40 mg) administration to 12 healthy young volunteers. Reference treatments were i.v. saline and GH-releasing hormone (GHRH; 1 microgram/kg). GH release (mean +/- SEM) after the i.v. dose of 1 microgram/kg hexarelin [area under the curve (AUC), 3175 +/- 506 micrograms/min.L] was about 2 times higher than that induced by 1 microgram/kg GHRH (AUC, 1544 +/- 161 micrograms/min.L; P < 0.001). Hexarelin (2 micrograms/kg, i.v.) elicited a further increase in GH levels (AUC, 4422 +/- 626 micrograms/min.L) compared to the 1 microgram/kg dose. The GH response to 2 micrograms/kg hexarelin, i.v., was very reproducible (AUC, 4016 +/- 563 vs. 3959 +/- 803 micrograms/min.L). The sc administration of hexarelin produced a dose-dependent GH response (AUC, 3180 +/- 392 and 4459 +/- 566 micrograms.min.L with 1.5 and 3 micrograms/kg, respectively). Intranasal administration of 20 micrograms/kg hexarelin induced GH release (AUC, 2642 +/- 452 micrograms/min.L) similar to that caused by 1 microgram/kg, i.v. Twenty and 40 mg hexarelin, po, produced a dose-related increase in GH levels (AUC, 2278 +/- 442 and 4079 +/- 514 micrograms/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 i.v. 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.
authors.affiliation: Department of Clinical Pathophysiology, University of Turin, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Ghigo
authors.forename: E
authors.initials: E
authors.lastname: Arvat
authors.forename: L
authors.initials: L
authors.lastname: Gianotti
authors.forename: B P
authors.initials: BP
authors.lastname: Imbimbo
authors.forename: V
authors.initials: V
authors.lastname: Lenaerts
authors.forename: R
authors.initials: R
authors.lastname: Deghenghi
authors.forename: F
authors.initials: F
authors.lastname: Camanni
mesh_terms: D000281:Administration, Intranasal; D000284:Administration, Oral; D000328:Adult; D005260:Female; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D009842:Oligopeptides / Q000008:administration & dosage / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood
chemical_list: D009842:Oligopeptides; C086184:hexarelin; D011388:Prolactin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone