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Oral activity of the growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 in rats, dogs and monkeys. 1990

R F Walker, and E E Codd, and F C Barone, and A H Nelson, and T Goodwin, and S A Campbell
Department of Toxicology, SmithKline Beecham Pharmaceuticals, King of Prussia, PA 19406-0939.

The purpose of this study was to evaluate the growth hormone (GH) releasing activity of orally administered His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 (GHRP-6, SK&F 110679) in rats, dogs and monkeys. Rats were administered GHRP-6 orally by gavage or parenterally through femoral artery catheters. Blood was collected before and after GHRP-6 administration for estimation of plasma GH and comparison of GH changes resulting from enteral and parenteral administration of the peptide. GHRP-6 was administered to dogs intravenously (i.v.) through cephalic vein catheters, intragastrically (i.g.) through esophagostomy tubes or intraduodenally (i.d.) through vascular access ports, and blood was collected before and after peptide administration for estimation of plasma GH. Cynomolgus monkeys were administered GHRP-6 i.g., and blood was collected from abdominal aorta for estimation of changes in plasma GH. Enteral activity of GHRP-6 was observed in all 3 species tested. In rats, ED50's for enteral and parenteral administration of GHRP-6 were 4 mg/kg and 28 micrograms/kg, respectively. Thus in rats, enterally administered GHRP-6 was 0.7% as bioactive as the parenterally administered peptide. In dogs GHRP-6 was slightly less potent than in rats, with ED50's for i.g. and i.v. administration approximately 15 mg/kg and 125 micrograms/kg, respectively. However, enteral potency of GHRP-6 in dogs was 0.8% of parenteral potency, and thus, comparable to that in rats. Additionally, comparison of plasma GH levels following i.g. vs i.d. administration in dogs suggested greater activity by the i.d. route. Monkeys were the species most sensitive to enterally administered GHRP-6, with plasma GH increased in those receiving i.g. doses as low as 0.3 mg/kg and an ED50 of 0.75 mg/kg compared to 4 and 15 mg/kg in rats and dogs, respectively. The results of this study demonstrate that GHRP-6 releases GH when administered directly into the gastrointestinal tract. Although enteral activity is approximately 1% of parenteral activity, GHRP-6 is potent, especially in primates which require relatively low doses to provoke GH release. These data suggest that orally active GHRP-6 may provide a practical therapeutic alternative to parenterally administered peptides such as GHRH, especially if enteral activity is enhanced with appropriate formulation.

UI MeSH Term Description Entries
D008252 Macaca fascicularis A species of the genus MACACA which typically lives near the coast in tidal creeks and mangrove swamps primarily on the islands of the Malay peninsula. Burmese Long-Tailed Macaque,Crab-Eating Monkey,Cynomolgus Monkey,M. f. aurea,M. fascicularis,Macaca fascicularis aurea,Monkey, Crab-Eating,Monkey, Cynomolgus,Crab-Eating Macaque,Burmese Long Tailed Macaque,Crab Eating Macaque,Crab Eating Monkey,Crab-Eating Macaques,Crab-Eating Monkeys,Cynomolgus Monkeys,Long-Tailed Macaque, Burmese,Macaque, Burmese Long-Tailed,Macaque, Crab-Eating,Monkey, Crab Eating
D008297 Male Males
D009842 Oligopeptides Peptides composed of between two and twelve amino acids. Oligopeptide
D011863 Radioimmunoassay Classic quantitative assay for detection of antigen-antibody reactions using a radioactively labeled substance (radioligand) either directly or indirectly to measure the binding of the unlabeled substance to a specific antibody or other receptor system. Non-immunogenic substances (e.g., haptens) can be measured if coupled to larger carrier proteins (e.g., bovine gamma-globulin or human serum albumin) capable of inducing antibody formation. Radioimmunoassays
D011919 Rats, Inbred Strains Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding. August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D004285 Dogs The domestic dog, Canis familiaris, comprising about 400 breeds, of the carnivore family CANIDAE. They are worldwide in distribution and live in association with people. (Walker's Mammals of the World, 5th ed, p1065) Canis familiaris,Dog
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004333 Drug Administration Routes The various ways of administering a drug or other chemical to a site in a patient or animal from where the chemical is absorbed into the blood and delivered to the target tissue. Administration Routes, Drug,Administration Route, Drug,Drug Administration Route,Route, Drug Administration,Routes, Drug Administration
D005260 Female Females
D000284 Administration, Oral The giving of drugs, chemicals, or other substances by mouth. Drug Administration, Oral,Administration, Oral Drug,Oral Administration,Oral Drug Administration,Administrations, Oral,Administrations, Oral Drug,Drug Administrations, Oral,Oral Administrations,Oral Drug Administrations

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