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

This study compared the pharmacokinetics of five peptidyl growth hormone secretagogues — ipamorelin (NNC 26-0161), NNC 26-0194, NNC 26-0235, GHRP-2, and GHRP-6 — in male rats using multiple routes of administration, with a particular focus on nasal delivery. Following intravenous bolus injection, all peptides showed biexponential plasma concentration decline. Ipamorelin stood out with a systemic plasma clearance approximately five times lower than GHRP-6. Excretion routes differed: ipamorelin was primarily cleared via urine, while GHRP-6 and the two NNC peptides were predominantly excreted in bile. Metabolic stability was moderate for ipamorelin and the NNC peptides, with 60–80% of administered doses recoverable as intact peptide from bile and urine combined. Intranasal bioavailability of ipamorelin was estimated at approximately 20%, while NNC 26-0235, NNC 26-0194, and GHRP-2 achieved approximately 50% nasal bioavailability. The authors concluded that nasal delivery appears to be a promising route for this peptide class. Key limitations include exclusive use of animal subjects (male rats), meaning findings may not directly translate to humans, and the study did not assess pharmacodynamic or safety endpoints.

Why this grade: All experiments were conducted exclusively in male rats; no human subjects or human-derived data were included, limiting direct clinical extrapolation.