Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormonesecretagogues with emphasis on nasal absorption

1. The pharmacokinetics of three new peptidyl growth hormone secretagogues, ipamorelin (NNC 26-0161), NNC 26-0194 and NNC 26-0235, were compared with two well-known hexapeptides, GHRP-2 and GHRP-6, in the male rat following d ifferent routes of administration. 2. Following i.v. bolus injection, plasma concentrations of the peptides de clined biexponentially. Ipamorelin differed markedly from the other peptide s investigated, demonstrating a systemic plasma clearance 5-fold lower than that of GHRP-6. Ipamorelin was mainly excreted in the urine, whereas GHRP- 6 was predominantly excreted in the bile. NNC 26-0194 and NNC 26-0235 also showed high biliary excretions. Ipamorelin and the two NNC peptides were mo derately resistant towards metabolism as 60-80 % of the administered dose c ould be recovered from bile and urine as intact peptide. 3. After intranasal application, the bioavailability of ipamorelin was esti mated at 20%. Higher bioavailabilities of similar to 50 % were determined f or NNC 26-0235, NNC 26-0194 and GHRP-2, whereas the nasal absorption of GHR P-6 was somewhat lower. Thus, the peptides could be easily transported acro ss the nasal epithelium suggesting that the nasal route seems promising for systemic delivery of this family of peptidyl growth hormone secretagogues.