Decapeptyl Mechanism of Action

Pharmacotherapeutic group: Gonadotropin releasing hormone analogues. ATC code: L02AE04.
Pharmacology: Pharmacodynamics: General: Triptorelin is a synthetic decapeptide analogue of the natural gonadotrophin-releasing hormone (GnRH). GnRH is a decapeptide, which is synthesised in the hypothalamus and regulates the biosynthesis and release of the gonadotrophins LH (luteinising hormone) and FSH (follicle stimulating hormone) by the pituitary. Triptorelin gives a greater stimulation of the pituitary to secrete LH and FSH than a comparable dose of gonadorelin, and has a longer duration of action. The increase of LH and FSH levels will initially lead to an increase of serum testosterone concentrations in men or serum estrogen concentrations in women. Chronic administration of a GnRH agonist results in an inhibition of pituitary LH- and FSH-secretion. The exact duration of action of DECAPEPTYL has not been established, but pituitary suppression is maintained for at least 6 days after stopping administration. After discontinuation of DECAPEPTYL, a further drop in circulating LH levels should be expected, with LH levels returning to baseline after approximately 2 weeks.
The triptorelin-induced downregulation of the pituitary can prevent the LH surge and thereby premature ovulation and/or follicular luteinization. The use of the downregulation with GnRH agonist reduces the cycle cancellation rate and improves the pregnancy rate in ART cycles.
Pharmacokinetics: The pharmacokinetic data suggest that after subcutaneous administration of DECAPEPTYL the systemic bioavailability of triptorelin is close to 100%. The elimination half-life of triptorelin is approximately 3-5 hours, indicating that triptorelin is eliminated within 24 hours. Metabolism to smaller peptides and amino acids primarily occurs in the liver and kidneys. Triptorelin is predominantly excreted in the urine.
Special populations: In patients with renal or hepatic impairment, triptorelin has a mean terminal half life of 7-8 hours compared to 3-5 hours in healthy subjects. The clinical studies indicated that the risk of accumulation of triptorelin in patients with severe liver and renal impairment is small.
Toxicology: Preclinical safety data: Short- and long-term nonclinical studies reveal no special hazards for humans. Changes in organ weights and lowering of plasma hormone concentrations were related to the pharmacological effect of triptorelin.
Life-long exposure to triptorelin had no carcinogenic effect on mice but caused species specific pituitary adenomas in rats. The rat finding was considered to be related to a rodent specific pharmacological effect of triptorelin and of no relevance to humans; no signs of mutagenicity, clastogenicity or carcinogenicity were recorded for triptorelin.
Reproductive toxicity studies in rats, rabbits and monkeys showed no toxic effects of treatment with triptorelin on fertility, embryo-fetal and pre- and postnatal development. Triptorelin is not teratogenic but there are indications for delayed fetal development and parturition in rats.