Goserelin

Goserelin
Clinical data
Trade names Zoladex
AHFS/Drugs.com Monograph
MedlinePlus a601002
Pregnancy
category
  • D (3.6mg) / X (10.8mg) (USA)
Routes of
administration		 implant
ATC code L02AE03 (WHO)
Legal status
Legal status
  • ℞ (Prescription only)
Pharmacokinetic data
Protein binding 27.3%
Biological half-life 4-5 hours
Excretion hepatic
Identifiers
Synonyms D-Ser(But)6Azgly10LHRH
CAS Number 65807-02-5 YesY
PubChem (CID) 5311128
IUPHAR/BPS 3879
DrugBank DB00014 YesY
ChemSpider 4470656 YesY
UNII 0F65R8P09N YesY
KEGG D04405 YesY
ChEBI CHEBI:5523 N
ChEMBL CHEMBL1201247 N
ECHA InfoCard 100.212.024
Chemical and physical data
Formula C59H84N18O14
Molar mass 1269.410 g/mol
3D model (Jmol) Interactive image
 NYesY (what is this?)  (verify)

Goserelin (INN, USAN, BAN) (brand name Zoladex, by AstraZeneca[1]), or goserelin acetate,[2][3] is a drug used to suppress production of the sex hormones (testosterone and estrogen), particularly in the treatment of breast and prostate cancer. It is an injectable gonadotropin releasing hormone superagonist (GnRH agonist), also known as a luteinizing hormone releasing hormone (LHRH) agonist.

Structurally, it is a decapeptide. It is the natural LHRH/GnRH decapeptide with two substitutions to inhibit rapid degradation.

Goserelin acetate stimulates the production of the sex hormones testosterone and estrogen in a non-pulsatile (non-physiological) manner. This causes the disruption of the endogenous hormonal feedback systems, resulting in the down-regulation of testosterone and estrogen production.

Zoladex was approved by the U.S. Food and Drug Administration in 1989[4] for treatment of prostate cancer.

Pharmacokinetics

Goserelin is a synthetic analogue of a naturally occurring luteinizing-hormone releasing hormone (LHRH). Bioavailability is almost complete. Goserelin is poorly protein bound and has a serum elimination half-life of two to four hours in patients with normal renal function. The half-life increases with patients with impaired renal function. There is no significant change in pharmacokinetics in subjects with liver failure. After administration, peak serum concentrations are reached in about two hours. It rapidly binds to the LHRH receptor cells in the pituitary gland thus leading to an initial increase in production of luteinizing hormone and thus leading to an initial increase in the production of corresponding sex hormones. This initial flare may be treated by co-prescribing/co-administering an androgen receptor antagonist such as bicalutamide (Casodex). Eventually, after a period of about 14–21 days, production of LH is greatly reduced due to receptor downregulation, and sex hormones are generally reduced to castrate levels.[5]

Indications

10.8mg implant syringe

Goserelin acetate is used to treat hormone-sensitive cancers of the breast (in pre- and peri-menopausal women) and prostate, and some benign gynaecological disorders (endometriosis, uterine fibroids and endometrial thinning). In addition, goserelin is used in assisted reproduction and in the treatment of precocious puberty. It may also be used in the treatment of male-to-female transgender people[6] and is favoured above other anti-androgens in some countries, such as the UK. It is available as a 1-month depot and a long-acting 3-month depot.

Dosage

Goserelin is administered by subcutaneous injection as an implant of 3.6mg or 10.8mg every 28 days for the duration of treatment.[7]

Side effects

Goserelin acetate may cause a temporary increase in bone pain and symptoms of prostatic cancer during the first few weeks of treatment. This is known as the tumour flare effect, and is the result of an initial increase in luteinizing hormone production, before the receptors are desensitised and hormonal production is inhibited. The symptoms will disappear, with hormonal inhibition. It is therefore advisable to co-treat with an antiandrogen during the first 2–3 weeks of goserelin treatment, particularly in patients with pre-existing bone symptoms.

Goserelin may cause bone pain, hot flushes, headache, stomach upset, depression, difficulty urinating (isolated cases), weight gain, swelling and tenderness of breasts (infrequent), decreased erections and reduced sexual desire. Bone pain can be managed symptomatically, and erectile dysfunction can be treated by Levitra (Vardenafil) or other similar oral therapies, although they will not treat the reduced sexual desire.

References

  1. ↑ AstraZeneca official Zoladex site
  2. ↑ Dictionary of Organic Compounds. CRC Press. pp. 3372–. ISBN 978-0-412-54090-5.
  3. ↑ I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 136–. ISBN 978-94-011-4439-1.
  4. ↑ FDA Approval for Zoladex 3.6 mg
  5. ↑ Kotake, Toshihiko; Michiyuki Usami; et al. (August 1999). "Goserelin Acetate with or without Antiandrogen or Estrogen in the Treatment of Patients with Advanced Prostate Cancer: a Multicenter, Randomized, Controlled Trial in Japan". Japanese Journal of Clin. Oncol. 29 (11): 562–570. doi:10.1093/jjco/29.11.562. ISSN 1465-3621. PMID 10678560. Retrieved 2007-02-26.
  6. ↑ Dittrich R, Binder H, Cupisti S, Hoffmann I, Beckmann MW, Mueller A. Endocrine treatment of male-to-female transsexuals using gonadotropin-releasing hormone agonist. Exp Clin Endocrinol Diabetes 2005;113:586–92.
  7. ↑ "Goserelin". NICE (National Institute for Health and Care Excellence). 2016. Retrieved 19 November 2016.


This article is issued from Wikipedia - version of the 11/19/2016. The text is available under the Creative Commons Attribution/Share Alike but additional terms may apply for the media files.