Pharmacokinetics of growth hormone-releasing hormone(1-29)-NH2 and stimulation of growth hormone secretion in healthy subjects after intravenous or intranasal administration.
The growth hormone-releasing hormone analogue GHRH(1-29)-NH2 was administered intravenously or intranasally to 30 healthy men aged 19-43 years. Intravenous injection of the lowest dose tested, 0.25 microgram/kg body weight, elicited significant release of growth hormone (GH). Maximal release (mean GH peaks of about 90 mU/l) was obtained with a dose of 1-2 micrograms/kg. Although GHRH(1-29)-NH2 was rapidly eliminated after intravenous injection, GH levels were elevated for about 3 hours. Absorption of GHRH(1-29)-NH2 through the nasal mucosa was found to be low, and the bioavailability was only 3-5%. There was a dose-dependent release of GH after intranasal administration of GHRH(1-29)-NH2, with the maximal response obtained with about 50 micrograms/kg; this dose was approximately as potent as 1 microgram/kg injected intravenously. The GH response after repeated intranasal administration of GHRH(1-29)-NH2 was sustained; there was no suppression of GH secretion during the night following a day when GHRH(1-29)-NH2 had been given three times intranasally. Based on these findings and the obvious convenience of intranasal administration compared with injections, it would be justified to test intranasal therapy for treatment of short stature in children with GH deficiency caused by hypothalamic damage.
Wilton
P
P
Department of Clinical Research, Kabi Pharmacia Peptide Hormones, Stockholm, Sweden.
Chardet
Y
Y
Danielson
K
K
Widlund
L
L
Gunnarsson
R
R
D000281:Administration, Intranasal; D000328:Adult; D001682:Biological Availability; D002940:Circadian Rhythm; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D013006:Growth Hormone / Q000097:blood / Q000187:drug effects*; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D017337:Sermorelin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics* / Q000494:pharmacology; D013997:Time Factors
D017337:Sermorelin; D013006:Growth Hormone