Pharmacokinetic-Pharmacodynamic Modeling of Ipamorelin, a Growth Hormone Releasing Peptide, in Human Volunteers
Gobburu JV, Agersø H, Jusko WJ, Ynddal L
Pharmaceutical Research (1999) · n=40
Ipamorelin's terminal half-life is roughly two hours and clearance is 0.078 L/h/kg — short enough that the GH pulse it produces is over within six hours, the pharmacological signature behind its 'physiological pulse' reputation.
This is the first published human pharmacokinetic-pharmacodynamic characterization of ipamorelin, conducted as a dose-escalation Phase 1 trial in Novo Nordisk's clinical pharmacology unit. Forty healthy male volunteers (eight per dose level) received a 15-minute intravenous infusion of ipamorelin at one of five doses: 4.21, 14.02, 42.13, 84.27, or 140.45 nmol/kg. Ipamorelin pharmacokinetics were dose-proportional across this 33-fold range, with a terminal half-life of 2 hours, systemic clearance of 0.078 L/h/kg, and a steady-state volume of distribution of 0.22 L/kg — values consistent with a small peptide cleared primarily by renal filtration and proteolysis. Growth hormone responses were modeled as an indirect-response system. After each dose, GH rose sharply to a peak at 0.67 hours and declined exponentially to negligible concentrations within roughly six hours at every dose. The model yielded an SC50 of 214 nmol/L (the ipamorelin plasma concentration producing half-maximal GH production) and a maximal GH production rate of 694 mIU/L/h. Inter-individual variability was larger on the pharmacodynamic side than on the pharmacokinetic side, consistent with biological differences in pituitary responsiveness rather than absorption or clearance heterogeneity.
This is a single-dose intravenous study in young healthy men — the population is not representative of the demographic that uses ipamorelin recreationally or clinically (older adults, mixed-sex, often with metabolic comorbidities), and intravenous dosing differs sharply from the subcutaneous route used in practice. No subcutaneous bioavailability or absorption rate is reported here. The dose-proportionality finding holds within the tested range but the highest dose (140.45 nmol/kg ≈ 1 mg in a 70-kg adult) is roughly five-fold above the typical "research" subcutaneous dose, so extrapolation downward is reasonable while extrapolation upward is not supported. The study reports GH dynamics over a single dose; tachyphylaxis with repeated dosing, which is well documented for ghrelin-receptor agonists in other studies, is outside its scope. Sponsorship by Novo Nordisk (developer of the molecule) is disclosed.
07·Member discussion
No member discussion yet.
Member-only conversation lives here — cycle notes, practitioner commentary, pattern-matching. Be the first paying member to start the thread.