Intranasal activity of the growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in conscious dogs.
This series of experiments was conducted to evaluate the growth hormone (GH) releasing activity of intranasally administered His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6, SK&F 110679) in conscious dogs. Intranasal administration of GHRP-6 increased plasma growth hormone levels in the conscious dog in a dose-related manner. Doses of 0.25 and 0.5 mg/kg produced GH levels of 11.3 +/- 4.8 ng/ml and 28.6 +/- 8.0 ng/ml, respectively. Peak levels were observed 15 minutes after dosing and GH levels were elevated for up to 105 minutes after intranasal dosing. Intranasal administration of isotonic saline did not produce any change in basal (negligable) GH levels. When GHRP-6 was given by the intravenous route, a maximal dose of 0.5 mg/kg, produced a peak plasma GH concentration of 60.8 +/- 10.5 ng/ml. Saline had no effect on GH levels when given intravenously. Using the intravenous and intranasal GH response data (i.e., area under the time-response curves), the intranasal bioavailability of GHRP-6 was estimated to be 34.4 to 44.9%. The results of these studies suggest that significant activity and excellent bioavailability can be achieved when GHRP-6 is administered by the intranasal route to conscious dogs. Based on these results, the intranasal activity of GHRP-6 should be evaluated in man. The successful intranasal administration of this peptide in man should provide GH therapy with reduced patient discomfort and better patient compliance when compared to presently available parenterally administered remedies.
Nelson
A H
AH
Department of Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.
Walker
R F
RF
Codd
E E
EE
Barone
F C
FC
D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D001682:Biological Availability; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D013006:Growth Hormone / Q000097:blood; D007262:Infusions, Intravenous; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000008:administration & dosage* / Q000493:pharmacokinetics
D009842:Oligopeptides; C041048:growth hormone releasing hexapeptide; D013006:Growth Hormone