Goserelin: Difference between revisions

| verifiedrevid = 407865148

| IUPAC_name = N-(21-((1H-indol-3-yl)methyl)-1,1-diamino-12-(tert-butoxymethyl)-6-(2-(2-carbamoylhydrazinecarbonyl)cyclopentanecarbonyl)-15-(4-hydroxybenzyl)-18-(hydroxymethyl)-25-(1H-imidazol-5-yl)-9-isobutyl-8,11,14,17,20,23-hexaoxo-2,7,10,13,16,19,22-heptaazapentacos-1-en-24-yl)-5-oxopyrrolidine-2-carboxamide

<!--Clinical data-->

| tradename = Zoladex

| pregnancy_category = D (3.6mg) / X (10.8mg) ([[United States|USA]])

| routes_of_administration = [[Implant (medicine)|implant]]

<!--Pharmacokinetic data-->

| elimination_half-life = 4-5 hours

| excretion = renal

<!--Identifiers-->

| ATC_prefix = L02

| ATC_suffix = AE03

| UNII_Ref = {{fdacite|changed|FDA}}

| ChEMBL = <!-- blanked - oldvalue: 1201247 -->

| C=59 | H=84 | N=18 | O=14

| molecular_weight = 1269.410 g/mol

| StdInChIKey_Ref = {{stdinchicite|correct|chemspider}}= {{stdinchicite|correct|chemspider}}

| synonyms = D-Ser(But)⁶Azgly¹⁰LHRH

'''Goserelin''' acetate (Zoladex, [[AstraZeneca]]<ref>[http://www.zoladex.net/ AstraZeneca official Zoladex site]</ref>) is an injectable [[gonadotropin releasing hormone]] [[superagonist]] ([[GnRH agonist]]), also known as a luteinizing hormone releasing hormone (LHRH) [[agonist]]. Structurally, it is a [[decapeptide]]. Goserelin acetate is used to suppress production of the sex hormones ([[testosterone]] and [[oestrogen]]), particularly in the treatment of breast and prostate cancer.

Goserelin acetate stimulates the production of the sex hormones testosterone and oestrogen 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 oestrogen production.

Zoladex approved by the U.S. Food and Drug Administration in 1989<ref>[http://www.fda.gov/medwatch/safety/1999/nov99.htm#zolade FDA Approval for Zoladex 3.6 mg]</ref> for treatment of prostate cancer.

==Pharmacokinetics==

Goserelin is a synthetic analogue of a naturally occurring luteinising-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 hepatic 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 [[Casodex]] (Bicalutamide) or similar medication. 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.<ref>{{cite journal | last = Kotake | first = Toshihiko | title = Goserelin Acetate with or without Antiandrogen or Estrogen in the Treatment of Patients with Advanced Prostate Cancer: a Multicenter, Randomized, Controlled Trial in Japan | journal = Japanese Journal of Clin. Oncol. | volume = 29 | issue = 11 | pages = 562–570 | date = August 1999 | url = http://jjco.oxfordjournals.org/cgi/content/full/29/11/562 | issn = 1465-3621 | accessdate = 2007-02-26 | doi = 10.1093/jjco/29.11.562 | pmid = 10678560 | author-separator = , | author2 = Michiyuki Usami | author3 = Hideyuki Akaza | display-authors = 2 | last4 = Koiso | first4 = K | last5 = Homma | first5 = Y | last6 = Kawabe | first6 = K | last7 = Aso | first7 = Y | last8 = Orikasa | first8 = S | last9 = Shimazaki | first9 = J }}</ref>

==Indications==

Goserelin Acetate is used to treat hormone-sensitive cancers of the [[breast cancer|breast]] (in pre- and peri- menopausal women) and [[prostate cancer|prostate]], and some benign gynaecological disorders ([[endometriosis]], [[uterine fibroid]]s and endometrial thinning). In addition, goserelin is used in [[assisted reproduction]] and in the treatment of [[precocious puberty]]. It is available as a 1-month depot and a long-acting 3-month depot.

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 Gosrelin treatment, particularly in patients with pre-existing bone symptoms. Goserelin may cause [[bone pain]], [[hot flushes]], [[headache]], [[Abdominal pain|stomach upset]], [[Depression (mood)|depression]], [[Urinary retention|difficulty urinating]] (isolated cases), [[weight gain]], [[Mastodynia|swelling and tenderness of breasts]] (infrequent), [[Erectile dysfunction|decreased erections]] and [[Libido#Libido_impairment|reduced sexual desire]]. Bone pain can be managed symptomatically, and decreased libido can be treated by [[Levitra]] ([[Vardenafil]]) or other similar oral therapies.

Memory loss may be severe and may not return to normal levels.<ref>Newton CR, Yuzpe AA, Timmon IS, Slota MD. Memory complaints: a side effect of continued exposure to gonadotropin-releasing hormone agonists (GnRHa). Paper presented at: Conjoint Annual Meetings of the American Fertility Society and the Canadian Fertility and Andrology Society; October 11–14, 1993; Montreal, Canada.</ref><ref>Friedman AJ, Juneau-Norcross M, Rein MS. Adverse effects of leuprolide acetate depot treatment. Fertil Steril. 1993;59(2):448-450.)</ref>

==References==

{{Reflist}}

==External links==

* [http://news.bbc.co.uk/1/hi/health/6320397.stm One man's experience of prostate cancer treatment using goserelin] - [[BBC News]]

{{Gonadotropins and GnRH}}

[[Category:AstraZeneca]]

[[Category:GnRH agonists]]

[[Category:Peptides]]

[[it:Goserelina]]

[[pl:Goserelina]]

[[pt:Gosserrelina]]