Tesamorelin Pharmacokinetics
Tesamorelin half-life, absorption, routes of administration, and clearance.
Tesamorelin Pharmacokinetics: The Short-Acting GHRH Analog
Tesamorelin has a plasma half-life of 26-38 minutes following subcutaneous injection, requiring once-daily administration to maintain therapeutic GH stimulation. Despite its rapid clearance, the trans-3-hexenoic acid N-terminal modification provides meaningful stability improvements over native GHRH, which is degraded by DPP-IV within seconds of release.
Rapid Absorption and Clearance
- Plasma half-life of 26-38 minutes after subcutaneous injection, substantially longer than native GHRH (which is degraded within seconds by DPP-IV) but still requiring daily dosing. • The trans-3-hexenoic acid modification at the N-terminus protects against rapid enzymatic degradation while preserving full GHRH receptor binding affinity. • Peak plasma concentration is reached within 15-30 minutes of SC injection, with the peptide cleared from circulation within approximately 3 hours. • Once-daily morning administration is the FDA-approved regimen (2 mg SC), timed to stimulate a physiological GH pulse without disrupting the natural nocturnal GH secretion pattern.
Physicochemical and PK profile
- Molecular Formula
- C221H366N72O67S
- Molecular Weight
- 5135.85 g/mol
- CAS Number
- 218949-48-5
- Half-Life
- 26-38 minutes
- Sequence
- Trans-3-hexenoic acid-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2
- Solubility
- Soluble in water
- Storage
- Refrigerate; reconstituted solution stable for 14 days at 2-8°C.
References
- Effects of tesamorelin on visceral fat in HIV-associated lipodystrophy
- Falutz J, et al. Metabolic effects of a growth hormone-releasing factor in patients with HIV. New England Journal of Medicine. 2007;357(23):2359-2370.
- Visceral fat reduction with tesamorelin is associated with improved liver enzymes in HIV.
- FDA prescribing information
- Falutz J, et al. Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat. Journal of Clinical Endocrinology & Metabolism. 2010;95(9):4291-4304.
- Predictors of Treatment Response to Tesamorelin, a Growth Hormone-Releasing Factor Analog, in HIV-Infected Patients with Excess Abdominal Fat.
- [PDF] Egrifta, 1 mg/vial. - accessdata.fda.gov
- Stanley TL, et al. Effect of tesamorelin on visceral fat and liver fat in HIV-infected patients with abdominal fat accumulation. JAMA. 2014;312(4):380-389.
- Effects of tesamorelin (TH9507), a growth hormone-releasing factor analog, in human immunodeficiency virus-infected patients with excess abdominal fat: a pooled analysis of two multicenter, double-blind placebo-controlled phase 3 trials with safety extension data.
- [PDF] SUMMARY REVIEW - accessdata.fda.gov
- Makimura H, et al. Effects of tesamorelin on cardiometabolic risk factors in HIV-infected patients. Journal of Clinical Endocrinology & Metabolism. 2011;96(9):2831-2838.
- Effects of tesamorelin on inflammatory markers in HIV patients with excess abdominal fat: relationship with visceral adipose reduction.
- Metabolic Effects of a Growth Hormone–Releasing Factor in Patients with HIV