Pharmacodynamic evaluation of a PEGylated analogue of human growth hormone releasing factor in rats and pigs.
D'Antonio. M M; Louveau. I I; Esposito. P P; Bertolino. M M; Canali. S S
Key Findings
- PEGylation (adding a 5 kDa PEG chain) dramatically prolongs the GH‑releasing effect of GRF‑1‑29 in rats (elevated AUC up to 48 h).
- Two extra GH peaks appear around 6 h and 8 h after injection, indicating a sustained release pattern.
- In pigs, both IV and subcutaneous administration of the PEG‑GRF raise endogenous GH and downstream IGF‑1 more than the unmodified peptide.
Practical Outcomes
- For self‑experimenters, a PEG‑linked GRF‑1‑29 could be dosed once daily (or possibly every other day) instead of multiple times per day, delivering more consistent GH and IGF‑1 spikes. Subcutaneous injection appears effective, which is convenient for self‑administration. However, human data are lacking, so start with low doses and monitor hormone levels closely.
Summary
A modified version of the growth‑hormone‑releasing peptide (GRF‑1‑29) that has a small PEG chain attached stays active in the body much longer than the regular peptide. In rats it kept GH levels high for up to 48 hours, and in pigs a single injection under the skin raised both GH and IGF‑1 for many hours. This means the PEG‑linked peptide could work with fewer doses and give steadier hormone spikes.
Abstract
The aim of this study was to assess the in vivo efficacy of monoPEGylated GRF(1-29)NH(2) having one PEG(5000) chains attached to either lysine 12 or 21 as compared to the GRF(1-29)NH(2) in rats and pigs. This analogue termed GRF-1PEG(5000) was tested after a single intravenous administration in rats and after a single intravenous or subcutaneous injection in pigs. After 1 h administration, GH concentrations returned to values close to controls in the group of rats injected with GRF(1-29)NH(2). In animals injected with the same dose of GRF-1PEG(5000), the AUC values corresponding to the whole period 0.5-48 h and particularly to the 0.5-8 h period were higher than in the placebo or in the GRF(1-29)NH(2) groups. Interestingly, two additional peaks were observed at about 6 and 8 h following administration. An increase in the response of the endogenous GH peaks was also observed in pigs administered GRF-1PEG(5000) by intravenous route. When GRF-1PEG(5000) was administered subcutaneously to pigs, a significant increase, as compared to placebo and GRF(1-29)NH(2,) in both GH and IGF-I levels was observed. This new analogue might find therapeutic application in paediatric growth hormone deficiency or in aging.
Study Information
pubmed
2004
10.1016/j.ghir.2003.12.014