Half-Life of Sermorelin (GHRH Analogue)
Sermorelin has a short half-life of approximately 10-20 minutes in humans. 1
Pharmacokinetic Profile
Sermorelin is a 29 amino acid analogue of human growth hormone-releasing hormone (GHRH) and is the shortest synthetic peptide that maintains the full biological activity of GHRH. Its pharmacokinetic profile is characterized by:
- Rapid elimination from circulation
- Primary clearance through renal ultrafiltration
- Enzymatic degradation at the N-terminus 1, 2
The short half-life of sermorelin significantly impacts its clinical application and administration requirements. After intravenous administration, sermorelin is rapidly eliminated, though its growth hormone-stimulating effects may persist for approximately 3 hours despite its quick clearance 3.
Route of Administration and Bioavailability
The pharmacokinetic properties of sermorelin vary by administration route:
- Intravenous administration: Provides 100% bioavailability with rapid onset of action
- Subcutaneous administration: Effective for therapeutic use, typically administered at bedtime
- Intranasal administration: Shows poor bioavailability (only 3-5%) compared to intravenous dosing 3
Clinical Implications of Short Half-Life
The short half-life of sermorelin has several important clinical implications:
Diagnostic use: The rapid and relatively specific stimulation of growth hormone makes sermorelin useful as a diagnostic test for growth hormone deficiency at a dose of 1 μg/kg bodyweight intravenously 1
Therapeutic dosing: For treatment purposes, sermorelin is typically administered as a once-daily subcutaneous injection of 30 μg/kg bodyweight at bedtime to maximize the natural pulsatile release of growth hormone 1
Pharmacodynamic effects: Despite its short half-life, sermorelin can produce sustained increases in height velocity in children with idiopathic growth hormone deficiency when administered appropriately 1
Attempts to Extend Half-Life
Due to the limitations imposed by sermorelin's short half-life, researchers have explored modifications to extend its duration of action:
- PEGylation (attachment of polyethylene glycol chains) has been investigated as a method to increase stability and prolong the half-life of sermorelin
- Mono-PEGylated isomers with PEG5000 polymer chains linked to specific lysine residues have shown promising biological activity while potentially extending the duration of action 2
Common Pitfalls in Clinical Use
When using sermorelin, clinicians should be aware of:
- The need for appropriate timing of administration (typically at night) to align with natural GH secretion patterns
- The importance of consistent administration due to its short half-life
- Potential false negative results when used diagnostically in patients with hypothalamic deficits 1
- Common side effects including transient facial flushing and injection site pain 1
Understanding sermorelin's short half-life is crucial for optimizing both its diagnostic and therapeutic applications in clinical practice.