Ipamorelin is a selective GH-Secretagogue and ghrelin receptor agonist. The potency of ghrelin stimulation can be compared to GHRP6 with less appetite stimulation properties. However, unlike other GH-Secretagogues this pentapeptide doesn’t release the same volumes of cortisol, acetylcholine, prolactin and aldosterone. It is for this reason Ipamorelin has been considered the first selective GH-Secretagogue.
‘Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers.’ – Gobburu JV, Agersø H, Jusko WJ, Ynddal L.
Source: Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, USA
Purpose: To examine the pharmacokinetics (PK) and pharmacodynamics (PD) of ipamorelin, a growth hormone (GH) releasing peptide, in healthy volunteers.
Methods: A trial was conducted with a dose escalation design comprising 5 different infusion rates (4.21, 14.02, 42.13, 84.27 and 140.45 nmol/kg over 15 minutes) with eight healthy male subjects at each dose level. Concentrations of ipamorelin and growth hormone were measured.
Results: The PK parameters showed dose-proportionality, with a short terminal half-life of 2 hours, a clearance of 0.078 L/h/kg and a volume of distribution at steady-state of 0.22 L/kg. The time course of GH stimulation by ipamorelin showed a single episode of GH release with a peak at 0.67 hours and an exponential decline to negligible GH concentration at all doses. The ipamorelin-GH concentration relationship was characterized using an indirect response model and population fitting. The model employed a zero-order GH release rate over a finite duration of time to describe the episodic release of GH. Ipamorelin induces the release of GH at all dose levels with the concentration (SC50) required for half-maximal GH stimulation of 214 nmol/L and a maximal GH production rate of 694 mIU/L/h. The inter-individual variability of the PD parameters was larger than that of the PK parameters.
Conclusions: The proposed PK/PD model provides a useful characterization of ipamorelin disposition and GH responses across a range of doses.