J V Gobburu1, H Agersø, W J Jusko, L Ynddal. 1. Department of Pharmaceutics, School of Pharmacy, State University of New York at Buffalo, 14260, USA.
Abstract
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.
RCT Entities:
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.
Authors: R G Smith; L H Van der Ploeg; A D Howard; S D Feighner; K Cheng; G J Hickey; M J Wyvratt; M H Fisher; R P Nargund; A A Patchett Journal: Endocr Rev Date: 1997-10 Impact factor: 19.871
Authors: K Raun; B S Hansen; N L Johansen; H Thøgersen; K Madsen; M Ankersen; P H Andersen Journal: Eur J Endocrinol Date: 1998-11 Impact factor: 6.664
Authors: Neil Benson; Joost de Jongh; Jonathan D Duckworth; Hannah M Jones; Henry E Pertinez; Jaiessh K Rawal; Tamara J van Steeg; Piet H Van der Graaf Journal: Antimicrob Agents Chemother Date: 2009-12-22 Impact factor: 5.191