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

• Published in: Xenobiotica 1998-11, Vol.28 (11), p.1083-1092
• Main Author: JOHANSEN, P. B.
• Format: Article
• Language: English
• Subjects: Absorption; Administration, Intranasal; Animals; Area Under Curve; Bile - chemistry; Biological and medical sciences; Biological Availability; Body Fluids - chemistry; Chromatography, High Pressure Liquid; Growth Hormone-Releasing Hormone - administration & dosage; Growth Hormone-Releasing Hormone - chemistry; Growth Hormone-Releasing Hormone - pharmacokinetics; Half-Life; hexapeptides; Hormones - administration & dosage; Hormones - chemistry; Hormones - pharmacokinetics; Hormones. Endocrine system; Injections, Intravenous; ipamorelin; Male; Medical sciences; Nasal Mucosa - metabolism; Oligopeptides - administration & dosage; Oligopeptides - chemistry; Oligopeptides - pharmacokinetics; Pharmacology. Drug treatments; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Urine - chemistry
• ISSN: 0049-8254; 1366-5928
• DOI: 10.1080/004982598238976

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 different routes of administration. 2. Following i.v. bolus injection, plasma concentrations of the peptides declined biexponentially. Ipamorelin differed markedly from the other peptides 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 moderately resistant towards metabolism as 60-80% of the administered dose could be recovered from bile and urine as intact peptide. 3. After intranasal application, the bioavailability of ipamorelin was estimated at ∼ 20%. Higher bioavailabilities of ∼ 50% were determined for NNC 26-0235, NNC 26- 0194 and GHRP-2, whereas the nasal absorption of GHRP-6 was somewhat lower. Thus, the peptides could be easily transported across the nasal epithelium suggesting that the nasal route seems promising for systemic delivery of this family of peptidyl growth hormone secretagogues.