Triptorelin

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Triptorelin
Triptorelin.svg
Clinical data
Trade names Decapeptyl, others
AHFS/Drugs.com Micromedex Detailed Consumer Information
License data
Routes of
administration 		Intramuscular
Drug class GnRH analogue; GnRH agonist; Antigonadotropin
ATC code
Legal status
Legal status
Pharmacokinetic data
Elimination half-life The elimination half-life for patients with hepatic impairment was similar to that of patients with renal impairment (geometric mean t(1/2, z): 6.6 h, 7.7 h and 7.6 h for Groups II, III and IV, respectively), but significantly longer than in healthy volunteers (2.8 h for Group I)

[3]

Triptorelin is a gonadotropin-releasing hormone (GnRH) analogue with enhanced affinity for GnRH receptors and a prolonged half-life due to its resistance to enzymatic degradation.
Excretion Kidney
Identifiers
  • 5-oxo-D-prolyl-L-histidyl-Ltryptophyl-L-seryl-Ltyrosyl-3-(1H-indol-2-yl)-L-alanylleucyl-L-arginyl-L-prolylglycinamide
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
CompTox Dashboard (EPA)
ECHA InfoCard 100.165.044 OOjs UI icon edit-ltr-progressive.svg
Chemical and physical data
Formula C64H82N18O13
Molar mass 1311.473 g·mol−1
3D model (JSmol)
  • CC(C)C[C@@H](C(=O)N[C@@H](CCCNC(=N)N)C(=O)N1CCC[C@H]1C(=O)NCC(=O)N)NC(=O)[C@@H](Cc2c[nH]c3c2cccc3)NC(=O)[C@H](Cc4ccc(cc4)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc5c[nH]c6c5cccc6)NC(=O)[C@H](Cc7cnc[nH]7)NC(=O)[C@@H]8CCC(=O)N8
  • InChI=1S/C64H82N18O13/c1-34(2)23-46(56(88)75-45(13-7-21-69-64(66)67)63(95)82-22-8-14-52(82)62(94)72-31-53(65)85)76-58(90)48(25-36-28-70-42-11-5-3-9-40(36)42)78-57(89)47(24-35-15-17-39(84)18-16-35)77-61(93)51(32-83)81-59(91)49(26-37-29-71-43-12-6-4-10-41(37)43)79-60(92)50(27-38-30-68-33-73-38)80-55(87)44-19-20-54(86)74-44/h3-6,9-12,15-18,28-30,33-34,44-52,70-71,83-84H,7-8,13-14,19-27,31-32H2,1-2H3,(H2,65,85)(H,68,73)(H,72,94)(H,74,86)(H,75,88)(H,76,90)(H,77,93)(H,78,89)(H,79,92)(H,80,87)(H,81,91)(H4,66,67,69)/t44-,45-,46-,47-,48+,49-,50-,51-,52-/m0/s1 X mark.svgN
  • Key:VXKHXGOKWPXYNA-PGBVPBMZSA-N X mark.svgN
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Triptorelin, sold under the brand name Decapeptyl among others, is a medication that acts as an agonist analog of gonadotropin-releasing hormone, repressing expression of luteinizing hormone (LH) and follicle-stimulating hormone (FSH). [4] [5]

Contents

It is a decapeptide (pGlu-His-Trp-Ser-Tyr-D-Trp-Leu-Arg-Pro-Gly-NH2) and a gonadotropin-releasing hormone agonist (GnRH agonist) used as the acetate or pamoate salts.

Primary indications include endometriosis, [6] for the reduction of uterine fibroids, to treat prostate cancer, and to treat male hypersexuality with severe sexual deviation. [5] The drug has also been used off label to delay puberty in patients with gender dysphoria. [7]

It was patented in 1975 and approved for medical use in 1986. [8] It is on the World Health Organization's List of Essential Medicines. [9]

Medical uses

Triptorelin is used to treat prostate cancer as part of androgen deprivation therapy. [10]

Another common use in the United Kingdom is for hormone replacement therapy to suppress testosterone or estrogen levels in transgender people (in conjunction with estradiol valerate for trans women or testosterone for trans men). Spironolactone and cyproterone acetate are other drugs used by trans people to suppress sex hormones, but these drugs have a completely different mechanism of action. [11] It can also be used as a puberty blocker [12] in the case of precocious puberty. [10]

Triptorelin has been used as a chemical castration agent for reducing sexual urges in sex offenders. [13]

Drug action

Triptorelin is a gonadorelin analogue, also known as luteinizing hormone releasing analogue (GnRH analogue, LHRH analogue). [4] The drug binds to receptors in the pituitary gland and stimulates secretion of gonadotropins (namely luteinizing hormone LH and follicle-stimulating hormone FSH). This causes an initial phase of LH and FSH stimulation, prior to down-regulation of the gonadotrophin-releasing hormone receptors, thereby reducing the release of gonadotropins in the long term, which in turn leads to the inhibition of androgen and estrogen production. [5]

Side-effects

General side effects can include: [5]

Society and culture

Brand names

Triptorelin is marketed under the brand names Decapeptyl (Ipsen) for treating prostate cancer, endometriosis, uterine myomas, and precocious puberty, [14] and Diphereline and Gonapeptyl (Ferring Pharmaceuticals). [15] In the United States, it is sold by Watson Pharmaceuticals as Trelstar [16] and by Arbor Pharmaceuticals as Triptodur (an extended-release 6-month depot injection). [17] In Iran, triptorelin is marketed under the brand name Variopeptyl. In the UK and Germany, it is sold as Salvacyl for the treatment of sexual deviations. [18]

History

Triptorelin was developed in Andrew V. Schally's lab at Tulane University. [19] Debiopharm licensed the drug from Tulane in 1982. [20]

Research

Triptorelin and other antiandrogens may be effective in the treatment of obsessive–compulsive disorder. [21]

Dosage in IVF treatment

Minimal daily dose of triptorelin acetate needed to suppress a premature LH surge during IVF treatment has been determined to be 15 microgram daily, and that 50 microg is equivalent to 100 microg in terms of IVF results. [22]

GnRHa doses used in IVF are derived from treatment

schedules used in disseminated prostate cancer, which aim at

complete gonadal suppression under all circumstances. Some

comparative studies indicate that the daily dose of agonist

used in IVF may be decreased without compromising the

results

The interval between initiation of study medication and start of FSH stimulation was defined as the desensitization phase.

For bothparameters, adjacent comparisons showed a statistically significant difference between the effect of placebo and 15 µgtriptorelin, but not between 15 and 50 µg, or between 50 and100 µg (Table II).

moreover, it appeared that a daily dose of 50 µg triptorelincreates a state of pituitary desensitization comparable with the ‘standard’ dose of 100 µg, and this endocrine finding was confirmed in the current study.

In prostate cancer

Modern assay technologies reveal that bilateral orchiectomy results in a serum T level of approximately 15 ng/dL as compared to the historical definition of castration of T < 50 ng/dL

Pharmacokinetics

Gonapeptyl Depot 3.75 mg

The systemic bioavailability of the active component triptorelin from the intramuscular depot is 38.3% in the first 13 days (2.9% per day). Further release is linear at 0.92% of the dose per day on average (34μg). Bioavailability after S.C. application is 69% of I.M. availability.

Plasma triptorelin values decreased to approx. 100 pg/ml before the next application after I.M. or S.C. application (median values).

References

  1. ↑ "Prescription medicines: registration of new chemical entities in Australia, 2015". Therapeutic Goods Administration (TGA). 21 June 2022. Retrieved 10 April 2023.
  2. ↑ "Triptodur- triptorelin kit". DailyMed. U.S. National Library of Medicine. 28 April 2022. Retrieved 15 May 2022.
  3. ↑ Müller, F. O.; Terblanchè, J.; Schall, R.; Van Zyl Smit, R.; Tucker, T.; Marais, K.; Groenewoud, G.; Porchet, H. C.; Weiner, M.; Hawarden, D. (1997). "Pharmacokinetics of triptorelin after intravenous bolus administration in healthy males and in males with renal or hepatic insufficiency". British Journal of Clinical Pharmacology. 44 (4): 335–341. doi:10.1046/j.1365-2125.1997.t01-1-00592.x. PMC   2042859 . PMID   9354307.
  4. 1 2 "gonadorelin analogue". Encyclopedia.com. Retrieved 2019-09-21.
  5. 1 2 3 4 Joint Formulary Committee (2018). British National Formulary (BNF) 70. London: Pharmaceutical Press. p. 635. ISBN   978-0-85711-173-9.
  6. ↑ Leone Roberti Maggiore U, Scala C, Remorgida V, Venturini PL, Del Deo F, Torella M, et al. (June 2014). "Triptorelin for the treatment of endometriosis". Expert Opinion on Pharmacotherapy. 15 (8). Informa Healthcare: 1153–1179. doi:10.1517/14656566.2014.916279. PMID   24832495. S2CID   23843087.
  7. ↑ Cohen D, Barnes H (September 2019). "Gender dysphoria in children: puberty blockers study draws further criticism". BMJ. 366: l5647. doi:10.1136/bmj.l5647. PMID   31540909. S2CID   202711942.
  8. ↑ Fischer J, Ganellin CR (2006). Analogue-based Drug Discovery. John Wiley & Sons. p. 514. ISBN   9783527607495.
  9. ↑ World Health Organization (2021). World Health Organization model list of essential medicines: 22nd list (2021). Geneva: World Health Organization. hdl: 10665/345533 . WHO/MHP/HPS/EML/2021.02.
  10. 1 2 "triptorelin (Intramuscular route)". Drugs.com. Retrieved 11 November 2016.
  11. ↑ Wylie KR, Fung Jr R, Boshier C, Rotchell M (2009). "Recommendations of endocrine treatment for patients with gender dysphoria". Sexual and Relationship Therapy. 24 (2): 175–187. doi:10.1080/14681990903023306. S2CID   20471537.
  12. ↑ Shumer DE, Nokoff NJ, Spack NP (August 2016). "Advances in the Care of Transgender Children and Adolescents". Advances in Pediatrics. 63 (1): 79–102. doi:10.1016/j.yapd.2016.04.018. PMC   4955762 . PMID   27426896.
  13. ↑ "Study: Drug effectively treats pedophilia". CNN . 11 February 1998. Archived from the original on 11 July 2021. Retrieved 8 July 2018.
  14. ↑ "Decapeptyl SR 11.25mg (triptorelin pamoate) - Patient Information Leaflet (PIL) - (emc)". www.medicines.org.uk. Retrieved 2022-11-14.
  15. ↑ "Gonapeptyl Depot 3.75 mg - Summary of Product Characteristics (SmPC) - (emc)". www.medicines.org.uk. Retrieved 2022-11-14.
  16. ↑ "Trelstar intramuscular: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing". WebMD. Retrieved 2022-11-14.
  17. ↑ "Triptodur Intramuscular: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing". WebMD. Retrieved 2022-11-14.
  18. ↑ "Salvacyl®, developed by Debiopharm, is launched in two European countries - a new therapeutic avenue for the treatment of sexual deviations". Debiopharm. 23 June 2009. Retrieved 2022-11-14.
  19. ↑ "About Us – Technology Transfer at Tulane University". Tulane University. Retrieved 4 January 2024.
  20. ↑ "Dr. Reddy's Launches Debiopharm's Pamorelin LA in India for the Treatment of Locally Advanced or Metastatic, Hormone-Dependent Prostate Cancer". Fierce Pharma. 7 December 2012. Retrieved 4 January 2024.
  21. ↑ Nomani H, Mohammadpour AH, Moallem SM, YazdanAbad MJ, Barreto GE, Sahebkar A (December 2019). "Anti-Androgen Drugs in the Treatment of Obsessive-Compulsive Disorder: A Systematic Review". Current Medicinal Chemistry. 27 (40): 6825–6836. doi:10.2174/0929867326666191209142209. PMID   31814547. S2CID   208956450.
  22. ↑ Janssens, R. M.; Lambalk, C. B.; Vermeiden, J. P.; Schats, R.; Bernards, J. M.; Rekers-Mombarg, L. T.; Schoemaker, J. (November 2000). "Dose-finding study of triptorelin acetate for prevention of a premature LH surge in IVF: a prospective, randomized, double-blind, placebo-controlled study". Human Reproduction (Oxford, England). 15 (11): 2333–2340. doi:10.1093/humrep/15.11.2333. ISSN   0268-1161. PMID   11056128.

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