Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers

Summary

Human pharmacokinetic and pharmacodynamic (PK/PD) study of ipamorelin in healthy male volunteers. Ipamorelin was given as 15-minute intravenous infusions at five escalating dose levels. Blood concentrations of ipamorelin and growth hormone (GH) were measured, and the relationship between them was described with a population PK/PD model.

Key Findings

• Pharmacokinetics were dose-proportional, with a short terminal half-life of 2 hours, clearance of 0.078 L/h/kg and a steady-state volume of distribution of 0.22 L/kg
• Each dose produced a single episode of GH release, peaking at 0.67 hours and declining exponentially to negligible GH concentrations
• Ipamorelin released GH at all dose levels; the concentration for half-maximal GH stimulation (SC50) was 214 nmol/L and the maximal GH production rate was 694 mIU/L/h
• Variability between individuals was larger for the GH response than for the pharmacokinetics
• An indirect response model with a zero-order GH release rate over a finite time described the episodic GH release

Methodology

Dose-escalation trial with five infusion rates (4.21, 14.02, 42.13, 84.27 and 140.45 nmol/kg over 15 minutes) and eight healthy male subjects at each dose level. Plasma ipamorelin and GH concentrations were measured and fitted with an indirect response model using population methods.

Limitations

• Intravenous infusion only; subcutaneous dosing was not studied
• Single doses; no repeated-dosing data
• Healthy men only
• The abstract reports only GH responses; it does not address cortisol, prolactin, side effects, or body composition

Relevance to Content

Core human data on how quickly ipamorelin acts and clears. A single IV dose produced one GH pulse that peaked at 0.67 hours and fell back to negligible levels, and the drug had a 2-hour terminal half-life. Useful for discussing timing, with the caveat that these results come from IV infusions, not subcutaneous injections.

See Also

• Parent compound: Ipamorelin