Jvs. Gobburu et al., Pharmacokinetic-pharmacodynamic modeling of ipamorelin, a growth hormone releasing peptide, in human volunteers, PHARM RES, 16(9), 1999, pp. 1412-1416
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 d
ifferent 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. Concentrat
ions of ipamorelin and growth hormone were measured.
Results. The PK parameters showed dose-proportionality, with a short termin
al half-life of 2 hours, a clearance of 0.078 L/h/kg and a volume of distri
bution at steady-state of 0.22 L/kg. The time course of GH stimulation by i
pamorelin showed a single episode of GH release with a peak at 0.67 hours a
nd an exponential decline to negligible GH concentration at all doses. The
ipamorelin-GH concentration relationship was characterized using an indirec
t response model and population fitting. The model employed a zero-order GH
release rate over a finite duration of time to describe the episodic relea
se 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 vari
ability 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.