Pharmacokinetic evaluation of ipamorelin and other peptidyl growth hormone secretagogues with emphasis on nasal absorption.
Johansen. P B PB; Hansen. K T KT; Andersen. J V JV; Johansen. N L NL
Key Findings
- Ipamorelin clears from the bloodstream about five times slower than GHRP‑6, indicating a longer systemic exposure.
- After intranasal dosing, ipamorelin shows ~20% bioavailability, while GHRP‑2 reaches ~50% bioavailability in rats.
- Both ipamorelin and the other tested peptides are moderately resistant to metabolism, with 60‑80% of the dose recovered intact in urine or bile.
Practical Outcomes
- Nasal administration could be a viable, non‑injectable way to use ipamorelin or GHRP‑2, but expect lower absorption for ipamorelin (~20%) compared to GHRP‑2 (~50%). The slower clearance of ipamorelin may allow less frequent dosing. These findings are from rats, so human dosing may differ and should be approached cautiously.
Summary
In rats, the peptide ipamorelin and related growth‑hormone‑releasing peptides stay in the blood longer than GHRP‑6 and are mostly cleared in urine. When sprayed into the nose, about 20% of ipamorelin and roughly 50% of GHRP‑2 get into the bloodstream, showing that nasal delivery can work for these peptides.
Abstract
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 approximately 20%. Higher bioavailabilities of approximately 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.
Study Information
pubmed
1998
10.1080/004982598238976
3
27