Buserelin: Difference between revisions

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==Medical uses==
==Medical uses==
Like other GnRH agonists, buserelin may be used in the treatment of [[hormone-responsive cancer]]s such as [[prostate cancer]] or [[breast cancer]], [[estrogen-dependent condition]]s (such as [[endometriosis]] or [[uterine fibroids]]), [[precocious puberty]], as a component of [[transgender hormone therapy]], and in [[reproductive technology|assisted reproduction]].<ref name="pmid2109679" /><ref name="pmid25387220">{{cite journal | vauthors = Wilczynski C, Emanuele MA | title = Treating a transgender patient: overview of the guidelines | journal = Postgrad Med | volume = 126 | issue = 7 | pages = 121–8 | year = 2014 | pmid = 25387220 | doi = 10.3810/pgm.2014.11.2840 | url = }}</ref> In [[ovulation induction]], it is used as a [[pituitary]] blockade as an adjunct to [[gonadotropin]] administration. It has also been studied for use as a [[hormonal contraceptive]] in women, with a 96% [[anovulation]] rate.<ref name="pmid2109679" />
Like other GnRH agonists, buserelin may be used in the treatment of [[hormone-responsive cancer]]s such as [[prostate cancer]] or [[breast cancer]], [[estrogen-dependent condition]]s (such as [[endometriosis]] or [[uterine fibroids]]), [[precocious puberty]], as a component of [[transgender hormone therapy]], and in [[reproductive technology|assisted reproduction]].<ref name="pmid2109679" /><ref name="pmid25387220">{{cite journal | vauthors = Wilczynski C, Emanuele MA | title = Treating a transgender patient: overview of the guidelines | journal = Postgrad Med | volume = 126 | issue = 7 | pages = 121–8 | year = 2014 | pmid = 25387220 | doi = 10.3810/pgm.2014.11.2840 | url = }}</ref> In [[ovulation induction]], it is used for [[pituitary gland|pituitary]] suppression as an [[adjunct therapy|adjunct]] to [[gonadotropin]] therapy.<ref name="pmid26558801">{{cite journal | vauthors = Siristatidis CS, Gibreel A, Basios G, Maheshwari A, Bhattacharya S | title = Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction | journal = Cochrane Database Syst Rev | volume = | issue = 11 | pages = CD006919 | year = 2015 | pmid = 26558801 | doi = 10.1002/14651858.CD006919.pub4 | url = }}</ref> It has also been studied for use as a [[hormonal contraceptive]] in women, with a 96% [[anovulation]] rate.<ref name="pmid2109679" />


==Side effects==
==Side effects==

Revision as of 11:19, 17 December 2017

Buserelin
Clinical data
Trade namesSuprefact, others
Other namesHoe-766; S-746766; D-Ser(tBu)6EA10-LHRH; 6-[O-(1,1-Dimethylethyl)-D-serine]-9-(N-ethyl-L-prolinamide)-10-deglycinamide-LHRH (pig)
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • X
Routes of
administration		Nasal spray, subcutaneous injection, subcutaneous implant[1][2]
Drug classGnRH analogue; GnRH agonist; Antigonadotropin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
Pharmacokinetic data
BioavailabilityOral: ineffective[1]
Intranasal: 2.5–3.3%[3]
Subcutaneous: 70%[1]
Protein binding15%[1]
MetabolismLiver, kidneys, gastrointestinal tract (pyroglutamyl peptidase, chymotrypsin-like endopeptidase)[1]
MetabolitesBuserelin (1–5)[4]
Elimination half-lifeIntravenous: 50–80 min[5]
Subcutaneous: 80 min[5]
Intranasal: 1–2 hours[5]
ExcretionUrine, bile[3][5]
Identifiers
CAS Number
PubChem CID
IUPHAR/BPS
DrugBank
ChemSpider
UNII
ChEMBL
ECHA InfoCard100.055.493 Edit this at Wikidata
Chemical and physical data
FormulaC60H86N16O13
Molar mass1239.42 g/mol g·mol−1
3D model (JSmol)
  • 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
  • InChI=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 checkY
  • Key:CUWODFFVMXJOKD-UVLQAERKSA-N checkY
 ☒NcheckY (what is this?)  (verify)

Buserelin, sold under the brand name Suprefact among others, is a medication which is used primarily in the treatment of prostate cancer and endometriosis.[3] It is also used in veterinary medicine.[6] The medication is typically used as a nasal spray, but is also available for use as a liquid or implant for injection into fat.[1][2]

Side effects of buserelin are related to sex hormone deprivation and include symptoms of low androgen levels and low estrogen levels such as hot flashes, sexual dysfunction, vaginal atrophy, and osteoporosis.[3][1] The drug is a gonadotropin-releasing hormone (GnRH) agonist and works by preventing the production of sex hormones by the gonads.[3][1]

Buserelin was first described in 1976 and was introduced for medical use in 1984.[7][8] It is not available in the United States, but is marketed widely elsewhere in the world.[9][6] It is available as a generic medication.[10][11]

Medical uses

Like other GnRH agonists, buserelin may be used in the treatment of hormone-responsive cancers such as prostate cancer or breast cancer, estrogen-dependent conditions (such as endometriosis or uterine fibroids), precocious puberty, as a component of transgender hormone therapy, and in assisted reproduction.[3][12] In ovulation induction, it is used for pituitary suppression as an adjunct to gonadotropin therapy.[13] It has also been studied for use as a hormonal contraceptive in women, with a 96% anovulation rate.[3]

Side effects

During the initial phase of the therapy, before GnRH receptors have been significantly down-regulated, testosterone levels are increased.[3][1] This can lead to transient tumour activation with bone pain (in patients with metastases) and urinary retention.[3][1] Side effects that occur later during the treatment are mainly due to low testosterone levels and include headache, hot flashes, reduced libido, and erectile dysfunction.[3][1]

Pharmacology

Pharmacodynamics

Buserelin is a GnRH agonist, or an agonist of the GnRH receptor.[3][1] 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.[3][1] 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.[3][1]

With chronic administration of buserelin however, the GnRH receptor becomes desensitized and stops responding completely both to buserelin and to endogenous GnRH.[3][1] 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 hence desensitization of the receptor.[3][1] 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.[3][1]

In men, approximately 95% of circulating testosterone is produced by the testes, with the remaining 5% being derived from the adrenal glands.[14] In accordance, GnRH analogues like buserelin can reduce testosterone levels by 95% in men.[14]

Pharmacokinetics

Buserelin is ineffective via oral administration due to first-pass metabolism by peptidases in the gastrointestinal tract.[1] Its bioavailability is 2.5 to 3.3% by intranasal administration and 70% by subcutaneous injection.[1] The plasma protein binding of buserelin is approximately 15%.[1] The metabolism of buserelin occurs in the liver, kidneys, and gastrointestinal tract and is mediated by peptidases, specifically pyroglutamyl peptidase and chymotrypsin-like endopeptidase.[1] The elimination half-life of buserelin regardless of route of administration is about 72 to 80 minutes.[1] Buserelin and its metabolites are eliminated in the urine and bile, with approximately 50% of buserelin excreted in the urine unchanged.[1][5]

Chemistry

Buserelin is a GnRH analogue, or a synthetic analogue of GnRH.[3][1] 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.[3][1][15] Buserelin is marketed for medical use in both its free alcohol (buserelin) and acetate salt (buserelin acetate) forms.[6]

History

Buserelin was first described in 1976 and was introduced for medical use in 1984.[7][8]

Society and culture

Generic names

Buserelin is the generic name of the drug and its INNTooltip International Nonproprietary Name and BANTooltip British Approved Name, while buserelin acetate is its USANTooltip United States Adopted Name, BANMTooltip British Approved Name, and JANTooltip Japanese Accepted Name, buséréline is its DCFTooltip Dénomination Commune Française, and buserelina is its DCITTooltip Denominazione Comune Italiana.[16][6][17][9]

Brand names

Buserelin is marketed by Sanofi-Aventis primarily under the brand names Suprefact, Suprefact Depot, and Suprecur.[6][9] It is also available under a number of other brand names including Bigonist, Bucel, Buserecur, Fuset, Metrelef, Profact, Profact Depot, Supremon, and Zerelin.[6][9] CinnaFact is a generic version of the medication that is produced by CinnaGen.[11] 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.[6][9]

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.[6][9][18] It is not available in the United States or Australia.[6][9][19]

See also

References

  1. ^ a b c d e f g h i j k l m n o p q r s t u v w x y http://products.sanofi.ca/en/suprefact.pdf
  2. ^ a b http://products.sanofi.ca/en/suprefact-depot.pdf
  3. ^ a b c d e f g h i j k l m n o p q r Brogden RN, Buckley MM, Ward A (1990). "Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile". Drugs. 39 (3): 399–437. doi:10.2165/00003495-199039030-00007. PMID 2109679.
  4. ^ K. Höffken (6 December 2012). Peptides in Oncology I: LH-RH Agonists and Antagonists. Springer Science & Business Media. pp. 77–. ISBN 978-88-470-2186-0.
  5. ^ a b c d e https://www.drugbank.ca/drugs/DB06719
  6. ^ a b c d e f g h i Index Nominum 2000: International Drug Directory. Taylor & Francis. 2000. pp. 149–. ISBN 978-3-88763-075-1.
  7. ^ a b Kuhl, H.; Kaplan, H.-G.; Taubert, H.-D. (1976). "Effects of a new analogue of LH-RH, D-Ser(TBU)6-EA10-LH-RH, on gonadotropin liberation in males". Deutsche Medizinische Wochenschrift. 101 (10): 361–364. doi:10.1055/s-0028-1104089. ISSN 0012-0472.
  8. ^ a b Annual Reports in Medicinal Chemistry. Academic Press. 8 September 1989. pp. 351–. ISBN 978-0-08-058368-6.
  9. ^ a b c d e f g https://www.drugs.com/international/buserelin.html
  10. ^ E Farkas; M Ryadnov (31 August 2013). Amino Acids, Peptide and Proteins. Royal Society of Chemistry. pp. 227–. ISBN 978-1-84973-585-8.
  11. ^ a b https://www.cinnagen.com/Product.aspx?t=2&l=1&Id=59&f=3
  12. ^ Wilczynski C, Emanuele MA (2014). "Treating a transgender patient: overview of the guidelines". Postgrad Med. 126 (7): 121–8. doi:10.3810/pgm.2014.11.2840. PMID 25387220.
  13. ^ Siristatidis CS, Gibreel A, Basios G, Maheshwari A, Bhattacharya S (2015). "Gonadotrophin-releasing hormone agonist protocols for pituitary suppression in assisted reproduction". Cochrane Database Syst Rev (11): CD006919. doi:10.1002/14651858.CD006919.pub4. PMID 26558801.
  14. ^ a b R.A.S Hemat (2 March 2003). Andropathy. Urotext. pp. 120–. ISBN 978-1-903737-08-8.
  15. ^ Tommaso Falcone; William W. Hurd (14 June 2017). Clinical Reproductive Medicine and Surgery: A Practical Guide. Springer. pp. 9–. ISBN 978-3-319-52210-4.
  16. ^ J. Elks (14 November 2014). The Dictionary of Drugs: Chemical Data: Chemical Data, Structures and Bibliographies. Springer. pp. 192–. ISBN 978-1-4757-2085-3.
  17. ^ I.K. Morton; Judith M. Hall (6 December 2012). Concise Dictionary of Pharmacological Agents: Properties and Synonyms. Springer Science & Business Media. pp. 57–. ISBN 978-94-011-4439-1.
  18. ^ https://health-products.canada.ca/dpd-bdpp/
  19. ^ "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Retrieved 17 December 2017.

Further reading

  • Roila F (1989). "Buserelin in the treatment of prostatic cancer". Biomed. Pharmacother. 43 (4): 279–85. PMID 2506941.
  • Trabant H, Widdra W, de Looze S (1990). "Efficacy and safety of intranasal buserelin acetate in the treatment of endometriosis: a review of six clinical trials and comparison with danazol". Prog. Clin. Biol. Res. 323: 357–82. PMID 2106146.
  • Brogden RN, Buckley MM, Ward A (1990). "Buserelin. A review of its pharmacodynamic and pharmacokinetic properties, and clinical profile". Drugs. 39 (3): 399–437. doi:10.2165/00003495-199039030-00007. PMID 2109679.

External links


Template:Signaling peptide/protein receptor modulators

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