Inside the body with Sermorelin

The approved presentations were an intravenous diagnostic dose and a subcutaneous daily regimen in children. Nasal absorption is poor (bioavailability about 3 to 5% in healthy men). Human subcutaneous bioavailability is not given in the sources we reviewed; in anaesthetised rats, plasma exposure after subcutaneous injection was about 4% of that after an intravenous injection, which suggests substantial degradation at the site or during absorption (animal-only finding).[src][src][src]

For human GHRH(1-44), plasma dipeptidyl-peptidase cleavage of the N-terminal Tyr-Ala gives GHRH(3-44)-NH2, which has less than 1/1000 of the activity; the in vivo half-life of GHRH(1-44) by HPLC was 6.8 min in normal subjects. Sermorelin shares the same N-terminus. A 2003 review reports its plasma half-life as roughly 10 to 20 minutes in humans, caused mostly by renal ultrafiltration and N-terminal enzymatic degradation, and an infusion study in men measured a disappearance half-time of 4.3 +/- 1.4 min (versus 6.7 +/- 0.5 min for a D-Ala2 analogue with reduced clearance).[src][src][src]

Sermorelin acts on the GHRH receptor, a class B GPCR that couples to Gs, on pituitary somatotrophs. The cryo-EM structure of the human receptor with Gs and full-length GHRH(1-44) (PDB 7CZ5) shows the natural ligand that sermorelin copies; sermorelin corresponds to residues 1 to 29 of that peptide. The structure is of the natural hormone, not of sermorelin.[src][src]

In a study of 30 healthy men aged 19 to 43 given GHRH(1-29)-NH2 intravenously or intranasally, intravenous doses gave dose-related GH release; despite rapid elimination of the peptide, GH remained elevated for about 3 hours. In eight slowly growing children, continuous subcutaneous infusion gave sustained pulsatile GH secretion without desensitisation for up to a year; the authors took the persisting pulses as evidence that somatostatin still sets the rhythm, so the body's own brake stays active.[src][src]

GH raises circulating IGF-I. In a small crossover study in 10 healthy old men, twice-daily subcutaneous GHRH(1-29) for 14 days raised mean 24-hour GH and IGF-I in a dose-related way (statistically significant only at the higher dose), and after the higher dose the values did not differ significantly from those of young men. In children treated for a year, IGF-I did not rise excessively. These are hormone markers, not proof of clinical benefit in adults.[src][src]

In the open-label study of 110 previously untreated prepubertal GH-deficient children (86 evaluable), mean height velocity rose from 4.1 +/- 0.9 cm/yr to 8.0 +/- 1.5 at 6 months and 7.2 +/- 1.3 at 12 months; 74% were classed as good responders at 6 months, and bone age advanced in proportion to height age. The 1999 review notes that effects on final adult height were not established and that increases in height velocity appeared smaller than with somatropin (indirect comparison). There is no equivalent proof of effect on body composition or ageing outcomes in adults.[src][src]