Buserelin

{{Short description|Chemical compound}} {{cs1 config|name-list-style=vanc|display-authors=6}} {{Drugbox | Verifiedfields = verified | Watchedfields = verified | verifiedrevid = 477165149 | IUPAC_name = (2''S'')-''N''-[(2''S'')-1-<nowiki>[[</nowiki>(2''S'')-1-<nowiki>[[</nowiki>(2''S'')-1-<nowiki>[[</nowiki>(2''S'')-1-<nowiki>[[</nowiki>(2''R'')-1-<nowiki>[[</nowiki>(2''S'')-1-<nowiki>[[</nowiki>(2''S'')-5-(diaminomethylideneamino)-1-[(2''S'')-2-(ethylcarbamoyl)pyrrolidin-1-yl]-1-oxopentan-2-yl]amino]-4-methyl-1-oxopentan-2-yl]amino]-3-[(2-methylpropan-2-yl)oxy]-1-oxopropan-2-yl]amino]-3-(4-hydroxyphenyl)-1-oxopropan-2-yl]amino]-3-hydroxy-1-oxopropan-2-yl]amino]-3-(1''H''-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1''H''-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide | image = Buserelin.svg | image_class = skin-invert-image | width = 225px | image2 = Buserelin molecule ball.png | image_class2 = bg-transparent | width2 = 235px

| tradename = Suprefact, others | Drugs.com = {{drugs.com|CONS|buserelin}} | pregnancy_category = X | legal_status = Rx-only | routes_of_administration = Nasal spray, subcutaneous injection, subcutaneous implant<ref name="SuprefactLabel" /><ref name="SuprefactDepotLabel" /> | class = GnRH analogue; GnRH agonist; Antigonadotropin

| bioavailability = Oral: ineffective<ref name="SuprefactLabel" /> Intranasal: 2.5–3.3%<ref name="pmid2109679" /> Subcutaneous: 70%<ref name="SuprefactLabel" /> | protein_bound = 15%<ref name="SuprefactLabel" /> | metabolism = Liver, kidneys, gastrointestinal tract (pyroglutamyl peptidase, chymotrypsin-like endopeptidase)<ref name="SuprefactLabel" /> | metabolites = Buserelin (1–5)<ref name="Höffken2012">{{cite book | vauthors = Höffken K |title=Peptides in Oncology I: LH-RH Agonists and Antagonists|url=https://books.google.com/books?id=q77tCAAAQBAJ&pg=PA77|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-88-470-2186-0|pages=77–|access-date=17 December 2017|archive-date=11 February 2022|archive-url=https://web.archive.org/web/20220211142302/https://books.google.com/books?id=q77tCAAAQBAJ&pg=PA77|url-status=live}}</ref> | elimination_half-life = Intravenous: 50–80 min<ref name="DrugsBank" /> Subcutaneous: 80 min<ref name="DrugsBank" /> Intranasal: 1–2 hours<ref name="DrugsBank" /> | excretion = Urine, bile<ref name="pmid2109679" /><ref name="DrugsBank">{{Cite web|url=https://www.drugbank.ca/drugs/DB06719|title=Buserelin|access-date=2017-12-17|archive-date=2018-03-12|archive-url=https://web.archive.org/web/20180312144126/https://www.drugbank.ca/drugs/DB06719|url-status=live}}</ref>

| CAS_number_Ref = {{cascite|correct|CAS}} | CAS_number = 57982-77-1 | CAS_supplemental = 68630-75-1 (acetate) | ATC_prefix = L02 | ATC_suffix = AE01 | ATC_supplemental = {{ATCvet|H01|CA90}} | PubChem = 50225 | IUPHAR_ligand = 3860 | DrugBank_Ref = {{drugbankcite|correct|drugbank}} | DrugBank = DB06719 | ChEBI_Ref = {{ebicite|correct|EBI}} | ChEBI = 135907 | ChEMBL_Ref = {{ebicite|correct|EBI}} | ChEMBL = 2110824 | ChemSpiderID_Ref = {{chemspidercite|correct|chemspider}} | ChemSpiderID = 45545 | UNII_Ref = {{fdacite|correct|FDA}} | UNII = PXW8U3YXDV | synonyms = Etilamide; HOE-766; HOE-766A; ICI-123215; S-746766; D-Ser(tBu)6EA10-LHRH; 6-[''O''-(1,1-Dimethylethyl)-D-serine]-9-(''N''-ethyl-L-prolinamide)-10-deglycinamide-LHRH (pig)

| C=60 | H=86 | N=16 | O=13 | SMILES = CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](COC(C)(C)C)NC(=O)[C@H](Cc2ccc(cc2)O)NC(=O)[C@H](CO)NC(=O)[C@H](Cc3c[nH]c4c3cccc4)NC(=O)[C@H](Cc5cnc[nH]5)NC(=O)[C@@H]6CCC(=O)N6 | StdInChI_Ref = {{stdinchicite|correct|chemspider}} | StdInChI = 1S/C60H86N16O13/c1-7-64-57(87)48-15-11-23-76(48)58(88)41(14-10-22-65-59(61)62)69-51(81)42(24-33(2)3)70-56(86)47(31-89-60(4,5)6)75-52(82)43(25-34-16-18-37(78)19-17-34)71-55(85)46(30-77)74-53(83)44(26-35-28-66-39-13-9-8-12-38(35)39)72-54(84)45(27-36-29-63-32-67-36)73-50(80)40-20-21-49(79)68-40/h8-9,12-13,16-19,28-29,32-33,40-48,66,77-78H,7,10-11,14-15,20-27,30-31H2,1-6H3,(H,63,67)(H,64,87)(H,68,79)(H,69,81)(H,70,86)(H,71,85)(H,72,84)(H,73,80)(H,74,83)(H,75,82)(H4,61,62,65)/t40-,41-,42-,43-,44-,45-,46-,47+,48-/m0/s1 | StdInChIKey_Ref = {{stdinchicite|correct|chemspider}} | StdInChIKey = CUWODFFVMXJOKD-UVLQAERKSA-N }}  '''Buserelin''', sold under the brand name '''Suprefact''' among others, is a medication which is used primarily in the treatment of prostate cancer and endometriosis.<ref name="pmid2109679">{{cite journal | vauthors = Brogden RN, Buckley MM, Ward A | title = Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile | journal = Drugs | volume = 39 | issue = 3 | pages = 399–437 | date = March 1990 | pmid = 2109679 | doi = 10.2165/00003495-199039030-00007 | s2cid = 195691965 }}</ref><ref name="SuprefactLabel" /><ref name="SuprefactDepotLabel" /> It is also used for other indications such as the treatment of premenopausal breast cancer, uterine fibroids, and early puberty, in assisted reproduction for female infertility, and as a part of transgender hormone therapy.<ref name="AdisInsight">{{Cite web|url=http://adisinsight.springer.com/drugs/800043601|title=Buserelin - Pharm-Sintez - AdisInsight|access-date=2017-12-17|archive-date=2017-12-24|archive-url=https://web.archive.org/web/20171224214316/http://adisinsight.springer.com/drugs/800043601|url-status=live}}</ref><ref name="pmid2109679" /><ref name="pmid25387220">{{cite journal | vauthors = Wilczynski C, Emanuele MA | title = Treating a transgender patient: overview of the guidelines | journal = Postgraduate Medicine | volume = 126 | issue = 7 | pages = 121–128 | date = November 2014 | pmid = 25387220 | doi = 10.3810/pgm.2014.11.2840 | s2cid = 22639336 }}</ref> In addition, buserelin is used in veterinary medicine.<ref name="IndexNominum2000" /> The medication is typically used as a nasal spray three times per day, but is also available for use as a solution or implant for injection into fat.<ref name="SuprefactLabel">{{Cite web|date=August 10, 2015|title=Suprefact - Buserelin Acetate (Product Monograph)|url=http://products.sanofi.ca/en/suprefact.pdf|website=Sanofi Aventis|access-date=December 17, 2017|archive-date=April 23, 2018|archive-url=https://web.archive.org/web/20180423203101/http://products.sanofi.ca/en/suprefact.pdf|url-status=live}}</ref><ref name="SuprefactDepotLabel">{{Cite web|date=August 10, 2015|title=Suprefact Depot 2 months and Suprefact Depot 3 months (Product Monograph)|url=http://products.sanofi.ca/en/suprefact-depot.pdf|website=Sanofi Aventis|access-date=December 17, 2017|archive-date=June 19, 2018|archive-url=https://web.archive.org/web/20180619011000/http://products.sanofi.ca/en/suprefact-depot.pdf|url-status=live}}</ref>

Side effects of buserelin are related to sex hormone deprivation and include symptoms of low testosterone levels and low estrogen levels such as hot flashes, sexual dysfunction, vaginal atrophy, and osteoporosis.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> Buserelin is a gonadotropin-releasing hormone agonist (GnRH agonist) and works by preventing the production of sex hormones by the gonads.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> It can lower sex hormone levels by about 95% in both sexes.<ref name="Hemat2003" /><ref name="Becker2001" /><ref name="CorsonDerman1995" /> Buserelin is a peptide and an analogue of {{abbrlink|GnRH|gonadotropin-releasing hormone}}.<ref name="Srivastava2017">{{cite book| vauthors = Srivastava V |title=Peptide-based Drug Discovery: Challenges and New Therapeutics|url=https://books.google.com/books?id=sbcpDwAAQBAJ&pg=PA182|date=26 June 2017|publisher=Royal Society of Chemistry|isbn=978-1-78262-732-6|pages=182–|access-date=6 January 2018|archive-date=28 October 2021|archive-url=https://web.archive.org/web/20211028140227/https://books.google.com/books?id=sbcpDwAAQBAJ&pg=PA182|url-status=live}}</ref>

Buserelin was first patented in 1974 and approved for medical use in 1985.<ref name=Fis2006>{{cite book | vauthors = Fischer J, Ganellin CR |title=Analogue-based Drug Discovery |date=2006 |publisher=John Wiley & Sons |isbn=978-3-527-60749-5 |page=514 |url=https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA514 |language=en |access-date=2020-09-19 |archive-date=2021-06-20 |archive-url=https://web.archive.org/web/20210620041512/https://books.google.com/books?id=FjKfqkaKkAAC&pg=PA514 |url-status=live }}</ref> It is not available in the United States, but is marketed widely elsewhere in the world, including in the United Kingdom, Canada, and many other countries.<ref name="Drugs.com" /><ref name="IndexNominum2000" /><ref name="DPD@HealthCanada" /> The medication is one of only two medically used GnRH analogues that are available as nasal sprays, the other being nafarelin.<ref name="Önerci2013">{{cite book| vauthors = Önerci TM |title=Nasal Physiology and Pathophysiology of Nasal Disorders|url=https://books.google.com/books?id=qfu8BAAAQBAJ&pg=PA208|date=17 August 2013|publisher=Springer Science & Business Media|isbn=978-3-642-37250-6|pages=208–|access-date=6 January 2018|archive-date=28 October 2021|archive-url=https://web.archive.org/web/20211028140224/https://books.google.com/books?id=qfu8BAAAQBAJ&pg=PA208|url-status=live}}</ref> Buserelin is available as a generic medication.<ref name="FarkasRyadnov2013">{{cite book | vauthors = Farkas E, Ryadnov M |title=Amino Acids, Peptide and Proteins|url=https://books.google.com/books?id=8NJGAgAAQBAJ&pg=PA227|date=31 August 2013|publisher=Royal Society of Chemistry|isbn=978-1-84973-585-8|pages=227–|access-date=17 December 2017|archive-date=11 February 2022|archive-url=https://web.archive.org/web/20220211142303/https://books.google.com/books?id=8NJGAgAAQBAJ&pg=PA227|url-status=live}}</ref><ref name="CinnaGen">{{Cite web|url=https://www.cinnagen.com/Product.aspx?t=2&l=1&Id=59&f=3|title=CinnaGen: CinnaFact|access-date=2017-12-17|archive-date=2018-01-06|archive-url=https://web.archive.org/web/20180106071856/https://www.cinnagen.com/Product.aspx?t=2&l=1&Id=59&f=3|url-status=live}}</ref>

==Medical uses== Buserelin is approved for the treatment of hormone-responsive cancers including prostate cancer and premenopausal breast cancer, sex hormone-dependent uterine diseases including endometrial hyperplasia, endometriosis, and uterine fibroids, and in assisted reproduction for female infertility.<ref name="AdisInsight"/><ref name="pmid2109679" /> It is also used off-label for the treatment of precocious puberty, as a puberty blocker in transgender children, and as a component of transgender hormone therapy.<ref name="pmid2109679" /><ref name="pmid25387220"/> In ovulation induction, buserelin is used for pituitary suppression as an adjunct to gonadotropin administration.<ref>{{cite journal | vauthors = Siristatidis CS, Yong LN, Maheshwari A, Ray Chaudhuri Bhatta S | title = Gonadotropin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction | journal = The Cochrane Database of Systematic Reviews | volume = 1 | article-number = CD006919 | date = January 2025 | pmid = 39783453 | doi = 10.1002/14651858.CD006919.pub5 }}</ref> It has also been assessed as a nasal spray for use as a hormonal contraceptive in women, with a 96% anovulation rate.<ref name="pmid2109679" />

===Dosages=== For prostate cancer, the dosage of buserelin by subcutaneous injection is 500 μg three times per day (once every 8 hours, 1,500 μg/day total) for one week and then 200 μg once daily thereafter.<ref name="MedBroadcast">{{cite web |url=https://medbroadcast.com/drug/getdrug/suprefact |title=Suprefact (buserelin acetate) |website=medbroadcast.com |access-date=2021-09-21 |archive-date=2021-09-21 |archive-url=https://web.archive.org/web/20210921210144/https://medbroadcast.com/drug/getdrug/suprefact |url-status=live }}</ref><ref name="NiederhuberArmitage2013">{{cite book| vauthors = Niederhuber JE, Armitage JO, Doroshow JH, Kastan MB, Tepper JE |title=Abeloff's Clinical Oncology E-Book|url=https://books.google.com/books?id=nQ4EAQAAQBAJ&pg=PA446|date=12 September 2013|publisher=Elsevier Health Sciences|isbn=978-1-4557-2881-7|pages=446–|access-date=6 January 2018|archive-date=11 February 2022|archive-url=https://web.archive.org/web/20220211142317/https://books.google.com/books?id=nQ4EAQAAQBAJ&pg=PA446|url-status=live}}</ref> If buserelin is used as a nasal spray, the dosage for prostate cancer is 800 μg sprayed into the nostrils three times per day (once every 8 hours, 2,400 μg/day total) for one week followed by 400 μg sprayed into the nostrils three times per day (once every 8 hours, 1,200 μg/day total) thereafter.<ref name="NiederhuberArmitage2013" /><ref name="MedBroadcast" /> For endometriosis, buserelin is used specifically as a nasal spray and the dosage is the same as that used for prostate cancer.<ref name="MedBroadcast" /> These dosages of buserelin for both subcutaneous injection and nasal spray have been found to decrease testosterone levels to near-castrate levels in men with prostate cancer, although suppression was more complete with subcutaneous injection presumably due to suboptimal absorption with intranasal administration.<ref name="pmid3087785">{{cite journal | vauthors = Rajfer J, Handelsman DJ, Crum A, Steiner B, Peterson M, Swerdloff RS | title = Comparison of the efficacy of subcutaneous and nasal spray buserelin treatment in suppression of testicular steroidogenesis in men with prostate cancer | journal = Fertility and Sterility | volume = 46 | issue = 1 | pages = 104–110 | date = July 1986 | pmid = 3087785 | doi = 10.1016/s0015-0282(16)49466-5 | doi-access = free }}</ref>

===Available forms=== Buserelin is available in the form of a 1 mg/mL solution for use as a nasal spray or subcutaneous injection once every 8 hours (three times per day) and as 6.3 mg and 9.45 mg implants for subcutaneous injection once every two and three months, respectively.<ref name="SuprefactLabel" /><ref name="SuprefactDepotLabel" /><ref name="Bansal2013">{{cite book| vauthors = Bansal K |title=Manual of Endometriosis|url=https://books.google.com/books?id=TpXU2m4TZEgC&pg=PA99|date=30 May 2013|publisher=JP Medical Ltd|isbn=978-93-5090-404-6|pages=99–|access-date=17 December 2017|archive-date=11 February 2022|archive-url=https://web.archive.org/web/20220211142309/https://books.google.com/books?id=TpXU2m4TZEgC&pg=PA99|url-status=live}}</ref><ref name="GrayWright2010">{{cite book| vauthors = Gray AH, Wright J, Goodey V, Bruce L | title=Injectable Drugs Guide|url=https://books.google.com/books?id=42TEmTJ0ewAC&pg=PA98|date=June 2010|publisher=Pharmaceutical Press|isbn=978-0-85369-787-9|pages=98–|access-date=2017-12-17|archive-date=2022-02-11|archive-url=https://web.archive.org/web/20220211142309/https://books.google.com/books?id=42TEmTJ0ewAC&pg=PA98|url-status=live}}</ref>

==Contraindications== Contraindications of buserelin include the following:<ref name="SuprefactLabel" /><ref name="SuprefactDepotLabel" />

* Hypersensitivity to buserelin or any of the other components of the medication (case reports of anaphylaxis exist) * Prostate cancer that is not hormone-dependent (as there will be no benefit from testosterone suppression) * Individuals who have undergone gonadectomy (as hormone levels will not be affected) * Pregnancy and breastfeeding (unknown whether buserelin might be teratogenic) * Undiagnosed abnormal vaginal bleeding

==Side effects== During the initial phase of the therapy, before GnRH receptors have been significantly downregulated, testosterone levels are increased.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> This can lead to transient tumor activation with bone pain (in patients with cancer metastases) and urinary retention.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> Side effects that occur later during the treatment are mainly due to low sex hormone levels and include reduced libido, erectile dysfunction, hot flashes, vaginal dryness, vaginal atrophy, menorrhagia, osteoporosis, depression, asthenia, emotional lability, headache, dizziness, and application site reactions.<ref name="pmid2109679" /><ref name="SuprefactLabel" />

==Overdose== Buserelin appears to be safe in the event of an overdose.<ref name="SuprefactLabel" /><ref name="SuprefactDepotLabel" />

==Pharmacology==

===Pharmacodynamics=== Buserelin is a GnRH agonist, or an agonist of the GnRH receptor.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> It is a superagonist of the GnRH receptor with potency for induction of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) secretion of about 20 to 170 times that of GnRH itself.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> By activating the GnRH receptor in the pituitary gland, buserelin induces the secretion of LH and FSH from the gonadotrophs of the anterior pituitary, which travel to the gonads through the bloodstream and activate gonadal sex hormone production as well as stimulate spermatogenesis in men and induce ovulation in women.<ref name="pmid2109679" /><ref name="SuprefactLabel" />

With chronic administration of buserelin however, the GnRH receptor becomes desensitized and completely stops responding both to buserelin and to endogenous GnRH.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> This is because GnRH is normally released from the hypothalamus in pulses, which keeps the GnRH receptor sensitive, whereas chronic buserelin administration results in more constant exposure and desensitization of the receptor.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> The profound desensitization of the GnRH receptor results in a loss of LH and FSH secretion from the anterior pituitary and a consequent shutdown of gonadal sex hormone production, markedly diminished or abolished spermatogenesis in men, and anovulation in women.<ref name="pmid2109679" /><ref name="SuprefactLabel" />

In men, approximately 95% of circulating testosterone is produced by the testes, with the remaining 5% being derived from the adrenal glands.<ref name="Hemat2003">{{cite book| vauthors = Hemat RA |title=Andropathy|url=https://books.google.com/books?id=hfwlDwAAQBAJ&pg=PA120|date=2 March 2003|publisher=Urotext|isbn=978-1-903737-08-8|pages=120–}}</ref> In accordance, GnRH analogues like buserelin can reduce testosterone levels by about 95% in men.<ref name="Hemat2003" /><ref name="pmid3087785"/> Sex hormone levels, including those of estradiol and progesterone, are similarly profoundly suppressed in premenopausal women.<ref name="Becker2001">{{cite book| vauthors = Becker KL |title=Principles and Practice of Endocrinology and Metabolism|url=https://books.google.com/books?id=FVfzRvaucq8C&pg=PA973|year=2001|publisher=Lippincott Williams & Wilkins|isbn=978-0-7817-1750-2|pages=973–}}</ref> The suppression of estradiol levels is 95% and progesterone levels are less than 1 ng/mL (normal range during the luteal phase approximately 10–20 ng/mL); the resulting levels are equivalent to those in postmenopausal women.<ref name="Becker2001" /><ref name="CorsonDerman1995">{{cite book| vauthors = Corson SL, Derman RJ |title=Fertility Control|url=https://books.google.com/books?id=30EzZPp1ypYC&pg=PA249|date=15 December 1995|publisher=CRC Press|isbn=978-0-9697978-0-7|pages=249–250}}</ref>

Buserelin has been found to suppress testosterone levels in men with prostate cancer from 426 ng/dL to 28 ng/dL (by 93.4%) with 200 μg by subcutaneous injection once per day and from 521 ng/dL to 53 ng/dL (by 89.8%) with 400 μg by nasal spray once every 8 hours (1,200 μg/day total).<ref name="pmid3133944">{{cite journal | vauthors = Soloway MS | title = Efficacy of buserelin in advanced prostate cancer and comparison with historical controls | journal = American Journal of Clinical Oncology | volume = 11 | issue = Suppl 1 | pages = S29–S32 | date = 1988 | pmid = 3133944 | doi = 10.1097/00000421-198812001-00006 | s2cid = 10101250 }}</ref> The difference in suppression may have been due to poor compliance.<ref name="pmid3133944" /> A few small studies have also assessed the suppression of testosterone levels with buserelin nasal spray twice a day instead of three times a day.<ref name="pmid6800852">{{cite journal | vauthors = Faure N, Labrie F, Lemay A, Bélanger A, Gourdeau Y, Laroche B, Robert G | title = Inhibition of serum androgen levels by chronic intranasal and subcutaneous administration of a potent luteinizing hormone-releasing hormone (LH-RH) agonist in adult men | journal = Fertility and Sterility | volume = 37 | issue = 3 | pages = 416–424 | date = March 1982 | pmid = 6800852 | doi = 10.1016/S0015-0282(16)46107-8 | doi-access = free }}</ref><ref name="pmid6411994">{{cite journal | vauthors = Tolis G, Faure N, Koutsilieris M, Lemay A, Klioze S, Yakabow A, Fazekas AT | title = Suppression of testicular steroidogenesis by the GnRH agonistic analogue Buserelin (HOE-766) in patients with prostatic cancer: studies in relation to dose and route of administration | journal = Journal of Steroid Biochemistry | volume = 19 | issue = 1C | pages = 995–998 | date = July 1983 | pmid = 6411994 | doi = 10.1016/0022-4731(83)90045-6 }}</ref> One such study found that testosterone levels in men with prostate cancer were suppressed during treatment with buserelin from 332 ng/dL to 215 ng/dL (28.9% lower than controls) with 200 μg by nasal spray twice a day (400 μg/day total), from 840 ng/dL to 182 ng/dL (71.4% lower than controls) with 500 μg by nasal spray twice a day (1,000 μg/day total), and from 598 ng/dL to 126 ng/dL (80.4% lower than controls) with 50 μg by subcutaneous injection once a day.<ref name="pmid6800852" />

===Pharmacokinetics=== Buserelin is ineffective via oral administration due to first-pass metabolism in the gastrointestinal tract.<ref name="SuprefactLabel" /> Its bioavailability is 2.5 to 3.3% by intranasal administration and 70% by subcutaneous injection.<ref name="SuprefactLabel" /> The plasma protein binding of buserelin is approximately 15%.<ref name="SuprefactLabel" /> The metabolism of buserelin occurs in the liver, kidneys, and gastrointestinal tract and is mediated by peptidases, specifically pyroglutamyl peptidase and chymotrypsin-like endopeptidase.<ref name="SuprefactLabel" /> The elimination half-life of buserelin regardless of route of administration is about 72 to 80 minutes.<ref name="SuprefactLabel" /> Buserelin and its metabolites are eliminated in urine and bile, with approximately 50% of buserelin excreted in urine unchanged.<ref name="SuprefactLabel" /><ref name="DrugsBank" />

==Chemistry== Buserelin is a GnRH analogue, or a synthetic analogue of GnRH.<ref name="pmid2109679" /><ref name="SuprefactLabel" /> It is a nonapeptide and is also known as [D-Ser(tBu)6,des-Gly-NH210]GnRH ethylamide or as D-Ser(tBu)6EA10-GnRH.<ref name="pmid2109679" /><ref name="SuprefactLabel" /><ref name="FalconeHurd2017">{{cite book| vauthors = Falcone T, Hurd WW |title=Clinical Reproductive Medicine and Surgery: A Practical Guide|url=https://books.google.com/books?id=pzgoDwAAQBAJ&pg=PA9|date=14 June 2017|publisher=Springer|isbn=978-3-319-52210-4|pages=9–|access-date=17 December 2017|archive-date=28 October 2021|archive-url=https://web.archive.org/web/20211028140237/https://books.google.com/books?id=pzgoDwAAQBAJ&pg=PA9|url-status=live}}</ref> Buserelin is marketed for medical use in both its free base (buserelin) and acetate salt (buserelin acetate) forms.<ref name="IndexNominum2000" />

==History== Buserelin was first described in 1976 and was introduced for medical use in 1984.<ref name="KuhlKaplan1976">{{cite journal | vauthors = Kuhl H, Kaplan HG, Taubert HD | title = [Effects of a new analogue of LH-RH, D-Ser(TBU)6- EA10-LH-RH, on gonadotropin liberation in males (author's transl)] | journal = Deutsche Medizinische Wochenschrift | volume = 101 | issue = 10 | pages = 361–364 | date = March 1976 | pmid = 129323 | doi = 10.1055/s-0028-1104089 | s2cid = 260086614 }}</ref><ref name="AcademicPress1984">{{cite book|title=Annual Reports in Medicinal Chemistry|url=https://books.google.com/books?id=HrALiG-4t7UC&pg=PA351|date=8 September 1989|publisher=Academic Press|isbn=978-0-08-058368-6|pages=351–|access-date=17 December 2017|archive-date=11 February 2022|archive-url=https://web.archive.org/web/20220211142309/https://books.google.com/books?id=HrALiG-4t7UC&pg=PA351|url-status=live}}</ref> Intranasal buserelin was the first GnRH agonist demonstrated to achieve medical castration in humans.<ref name="pmid24825748">{{cite journal | vauthors = Labrie F | title = GnRH agonists and the rapidly increasing use of combined androgen blockade in prostate cancer | journal = Endocrine-Related Cancer | volume = 21 | issue = 4 | pages = R301–R317 | date = August 2014 | pmid = 24825748 | doi = 10.1530/ERC-13-0165 | doi-access = free }}</ref> This was initially observed via a marked decrease in circulating testosterone levels in a single patient in 1980.<ref name="pmid24825748" />

==Society and culture==

===Generic names=== ''Buserelin'' is the generic name of the drug and its {{abbrlink|INN|International Nonproprietary Name}} and {{abbrlink|BAN|British Approved Name}}, while ''buserelin acetate'' is its {{abbrlink|USAN|United States Adopted Name}}, {{abbrlink|BANM|British Approved Name}}, and {{abbrlink|JAN|Japanese Accepted Name}}, ''buséréline'' is its {{abbrlink|DCF|Dénomination Commune Française}}, and ''buserelina'' is its {{abbrlink|DCIT|Denominazione Comune Italiana}}.<ref name="Elks2014">{{cite book| vauthors = Elks J |title=The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies|url=https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA192|date=14 November 2014|publisher=Springer|isbn=978-1-4757-2085-3|pages=192–|access-date=17 December 2017|archive-date=12 March 2017|archive-url=https://web.archive.org/web/20170312135341/https://books.google.com/books?id=0vXTBwAAQBAJ&pg=PA192|url-status=live}}</ref><ref name="IndexNominum2000">{{cite book|title=Index Nominum 2000: International Drug Directory|url=https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA149|year=2000|publisher=Taylor & Francis|isbn=978-3-88763-075-1|pages=149–|access-date=2017-12-17|archive-date=2017-03-12|archive-url=https://web.archive.org/web/20170312135358/https://books.google.com/books?id=5GpcTQD_L2oC&pg=PA149|url-status=live}}</ref><ref name="MortonHall2012">{{cite book| vauthors = Morton IK, Hall JM |title=Concise Dictionary of Pharmacological Agents: Properties and Synonyms|url=https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA57|date=6 December 2012|publisher=Springer Science & Business Media|isbn=978-94-011-4439-1|pages=57–|access-date=17 December 2017|archive-date=12 March 2017|archive-url=https://web.archive.org/web/20170312135609/https://books.google.com/books?id=tsjrCAAAQBAJ&pg=PA57|url-status=live}}</ref><ref name="Drugs.com">{{Cite web|url=https://www.drugs.com/international/buserelin.html|title=Buserelin|access-date=2017-12-17|archive-date=2018-01-06|archive-url=https://web.archive.org/web/20180106064718/https://www.drugs.com/international/buserelin.html|url-status=live}}</ref> While under development by Hoechst AG, buserelin was also known as ''HOE-766''.<ref name="Elks2014" /><ref name="IndexNominum2000" /><ref name="MortonHall2012" /><ref name="Drugs.com" />

===Brand names=== Buserelin is marketed by Sanofi-Aventis primarily under the brand names Suprefact, Suprefact Depot, and Suprecur.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> It is also available under a number of other brand names including Bigonist, Bucel, Buserecur, Fuset, Metrelef, Profact, Profact Depot, Supremon, and Zerelin.<ref name="IndexNominum2000" /><ref name="Drugs.com" /> CinnaFact is a generic version of the medication that is produced by CinnaGen.<ref name="CinnaGen" /> Buserelin is marketed for use in veterinary medicine primarily under the brand name Receptal, but is also available under the brand names Buserol, Busol, Porceptal, and Veterelin.<ref name="IndexNominum2000" /><ref name="Drugs.com" />

===Availability=== Buserelin is marketed in the United Kingdom, Ireland, other European countries, Canada, New Zealand, and South Africa, as well as in Latin America, Asia, and elsewhere in the world.<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="DPD@HealthCanada">{{Cite web|url = https://health-products.canada.ca/dpd-bdpp/|title = Drug Product Database Online Query|date = 25 April 2012|access-date = 17 December 2017|archive-date = 29 October 2020|archive-url = https://web.archive.org/web/20201029232807/https://health-products.canada.ca/dpd-bdpp/|url-status = live}}</ref> It is not available in the United States or Australia.<ref name="IndexNominum2000" /><ref name="Drugs.com" /><ref name="Drugs@FDA">{{cite web |title=Drugs@FDA: FDA Approved Drug Products |publisher=United States Food and Drug Administration |access-date=17 December 2017 |url=https://www.accessdata.fda.gov/scripts/cder/daf/ |archive-date=16 November 2016 |archive-url=https://web.archive.org/web/20161116164727/http://www.accessdata.fda.gov/scripts/cder/daf/ |url-status=live }}</ref>

==Research== The steroidal antiandrogen cyproterone acetate has been studied for blocking the testosterone flare at the start of buserelin therapy in men with prostate cancer.<ref name="DenisGriffiths1999">{{cite book| vauthors = Denis LJ, Griffiths K, Kaisary AV, Murphy GP |title=Textbook of Prostate Cancer: Pathology, Diagnosis and Treatment: Pathology, Diagnosis and Treatment|url=https://books.google.com/books?id=GreZlojD-tYC&pg=PA308|date=1 March 1999|publisher=CRC Press|isbn=978-1-85317-422-3|pages=308–|access-date=25 December 2017|archive-date=8 February 2021|archive-url=https://web.archive.org/web/20210208015234/https://books.google.com/books?id=GreZlojD-tYC&pg=PA308|url-status=live}}</ref><ref name="KlosterhalfenJacobi1988">{{cite book| vauthors = Klosterhalfen H, Jacobi GH | veditors = Klosterhalfen H |title=Endocrine Management of Prostatic Cancer|chapter=Long-term results of an LH-RH agonist monotherapy in patients with carcinoma of the prostate and reflections on the so-called total androgen blockade with pre-medicated cyproterone acetate|year=1988|pages=127–137|doi=10.1515/9783110853674-014|isbn=978-3-11-085367-4}}</ref> While cyproterone acetate for two weeks eliminates the biological and biochemical signs of the flare, no benefits on prostate cancer outcomes were observed.<ref name="DenisGriffiths1999" />

Very low doses of buserelin nasal spray have been assessed for increasing testosterone levels and fertility in men with oligoasthenozoospermia and hypogonadotropic hypogonadism.<ref name="pmid9712445">{{cite journal | vauthors = Matsumiya K, Kitamura M, Kishikawa H, Kondoh N, Fujiwara Y, Namiki M, Okuyama A | title = A prospective comparative trial of a gonadotropin-releasing hormone analogue with clomiphene citrate for the treatment of oligoasthenozoospermia | journal = International Journal of Urology | volume = 5 | issue = 4 | pages = 361–363 | date = July 1998 | pmid = 9712445 | doi = 10.1111/j.1442-2042.1998.tb00367.x | s2cid = 24680327 }}</ref><ref name="pmid19591988">{{cite journal | vauthors = Iwamoto H, Yoshida A, Suzuki H, Tanaka M, Watanabe N, Nakamura T | title = A man with hypogonadotropic hypogonadism successfully treated with nasal administration of the low-dose gonadotropin-releasing hormone analog buserelin | journal = Fertility and Sterility | volume = 92 | issue = 3 | pages = 1169.e1–1169.e3 | date = September 2009 | pmid = 19591988 | doi = 10.1016/j.fertnstert.2009.05.090 | doi-access = free }}</ref>

== References == {{Reflist|35em}}

== Further reading == {{refbegin}} * {{cite journal | vauthors = Roila F | title = Buserelin in the treatment of prostatic cancer | journal = Biomedicine & Pharmacotherapy | volume = 43 | issue = 4 | pages = 279–285 | year = 1989 | pmid = 2506941 | doi = 10.1016/0753-3322(89)90009-7 }} * {{cite journal | vauthors = Trabant H, Widdra W, de Looze S | title = Efficacy and safety of intranasal buserelin acetate in the treatment of endometriosis: a review of six clinical trials and comparison with danazol | journal = Progress in Clinical and Biological Research | volume = 323 | pages = 357–382 | year = 1990 | pmid = 2106146 }} * {{cite journal | vauthors = Brogden RN, Buckley MM, Ward A | title = Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile | journal = Drugs | volume = 39 | issue = 3 | pages = 399–437 | date = March 1990 | pmid = 2109679 | doi = 10.2165/00003495-199039030-00007 | s2cid = 195691965 }} {{refend}}

== External links == * [http://adisinsight.springer.com/drugs/800043601 Buserelin - AdisInsight]

Category:Gonadotropin-releasing hormone agonists Category:Hormonal antineoplastic drugs Category:Nonapeptides Category:Puberty blockers Category:World Anti-Doping Agency prohibited substances