Buserelin

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Buserelin
Clinical data
Trade namesSuprefact, others
Other namesEtilamide; 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)
AHFS/Drugs.comMicromedex Detailed Consumer Information
Pregnancy
category
  • X
GnRH agonist; Antigonadotropin
ATC code
Legal status
Legal status
  • In general: ℞ (Prescription only)
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
  • (2S)-N-[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2R)-1-[[(2S)-1-[[(2S)-5-(diaminomethylideneamino)-1-[(2S)-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-(1H-indol-3-yl)-1-oxopropan-2-yl]amino]-3-(1H-imidazol-5-yl)-1-oxopropan-2-yl]-5-oxopyrrolidine-2-carboxamide
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
  (verify)

Buserelin, sold under the brand name Suprefact among others, is a

injection into fat.[1][2]

analogue of GnRHTooltip gonadotropin-releasing hormone.[12]

Buserelin was first patented in 1974 and approved for medical use in 1985.

generic medication.[17][18]

Medical uses

Buserelin is approved for the treatment of

hormonal contraceptive in women, with a 96% anovulation rate.[3]

Dosages

For prostate cancer, the dosage of buserelin by

intranasal administration.[22]

Available forms

Buserelin is available in the form of a 1 mg/mL

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.[1][2][23][24]

Contraindications

Contraindications of buserelin include the following:[1][2]

  • 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)
  • teratogenic
    )
  • Undiagnosed
    abnormal vaginal bleeding

Side effects

During the initial phase of the therapy, before GnRH receptors have been significantly

asthenia, emotional lability, headache, dizziness, and application site reactions.[3][1]

Overdose

Buserelin appears to be safe in the event of an

overdose.[1][2]

Pharmacology

Pharmacodynamics

Buserelin is a GnRH agonist, or an

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

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 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.[9] In accordance, GnRH analogues like buserelin can reduce testosterone levels by about 95% in men.[9][22] Sex hormone levels, including those of estradiol and progesterone, are similarly profoundly suppressed in premenopausal women.[10] 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.[10][11]

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).[25] The difference in suppression may have been due to poor compliance.[25] 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.[26][27] 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.[26]

Pharmacokinetics

Buserelin is ineffective via

elimination half-life of buserelin regardless of route of administration is about 72 to 80 minutes.[1] Buserelin and its metabolites are eliminated in urine and bile, with approximately 50% of buserelin excreted in urine unchanged.[1][5]

Chemistry

Buserelin 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][28] Buserelin is marketed for medical use in both its free base (buserelin) and acetate salt (buserelin acetate) forms.[8]

History

Buserelin was first described in 1976 and was introduced for medical use in 1984.[29][30] Intranasal buserelin was the first GnRH agonist demonstrated to achieve medical castration in humans.[31] This was initially observed via a marked decrease in circulating testosterone levels in a single patient in 1980.[31]

Society and culture

Generic names

Buserelin is the

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.[32][8][33][14] While under development by Hoechst AG, buserelin was also known as HOE-766.[32][8][33][14]

Brand names

Buserelin is marketed by

CinnaGen.[18] 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.[8][14]

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.[8][14][15] It is not available in the United States or Australia.[8][14][34]

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.[35][36] While cyproterone acetate for two weeks eliminates the biological and biochemical signs of the flare, no benefits on prostate cancer outcomes were observed.[35]

Very low doses of buserelin nasal spray have been assessed for increasing testosterone levels and fertility in men with

oligoasthenozoospermia and hypogonadotropic hypogonadism.[37][38]

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 z aa ab ac "Suprefact - Buserelin Acetate (Product Monograph)" (PDF). Sanofi Aventis. August 10, 2015. Archived (PDF) from the original on April 23, 2018. Retrieved December 17, 2017.
  2. ^ a b c d e f "Suprefact Depot 2 months and Suprefact Depot 3 months (Product Monograph)" (PDF). Sanofi Aventis. August 10, 2015. Archived (PDF) from the original on June 19, 2018. Retrieved December 17, 2017.
  3. ^
    S2CID 195691965
    .
  4. ISBN 978-88-470-2186-0. Archived
    from the original on 11 February 2022. Retrieved 17 December 2017.
  5. ^ a b c d e "Buserelin". Archived from the original on 2018-03-12. Retrieved 2017-12-17.
  6. ^ a b "Buserelin - Pharm-Sintez - AdisInsight". Archived from the original on 2017-12-24. Retrieved 2017-12-17.
  7. ^
    S2CID 22639336
    .
  8. ^
    ISBN 978-3-88763-075-1. Archived
    from the original on 2017-03-12. Retrieved 2017-12-17.
  9. ^
    ISBN 978-1-903737-08-8
    .
  10. ^
    ISBN 978-0-7817-1750-2
    .
  11. ^
    ISBN 978-0-9697978-0-7
    .
  12. ISBN 978-1-78262-732-6. Archived
    from the original on 28 October 2021. Retrieved 6 January 2018.
  13. ISBN 978-3-527-60749-5. Archived
    from the original on 2021-06-20. Retrieved 2020-09-19.
  14. ^ a b c d e f g h "Buserelin". Archived from the original on 2018-01-06. Retrieved 2017-12-17.
  15. ^ a b "Drug Product Database Online Query". 25 April 2012. Archived from the original on 29 October 2020. Retrieved 17 December 2017.
  16. ISBN 978-3-642-37250-6. Archived
    from the original on 28 October 2021. Retrieved 6 January 2018.
  17. ISBN 978-1-84973-585-8. Archived
    from the original on 11 February 2022. Retrieved 17 December 2017.
  18. ^ a b "CinnaGen: CinnaFact". Archived from the original on 2018-01-06. Retrieved 2017-12-17.
  19. PMID 26558801. Archived
    from the original on 2022-02-11. Retrieved 2019-09-24.
  20. ^ a b c "Suprefact (buserelin acetate)". medbroadcast.com. Archived from the original on 2021-09-21. Retrieved 2021-09-21.
  21. ^
    ISBN 978-1-4557-2881-7. Archived
    from the original on 11 February 2022. Retrieved 6 January 2018.
  22. ^
    PMID 3087785
    .
  23. ISBN 978-93-5090-404-6. Archived
    from the original on 11 February 2022. Retrieved 17 December 2017.
  24. ISBN 978-0-85369-787-9. Archived
    from the original on 2022-02-11. Retrieved 2017-12-17.
  25. ^
    S2CID 10101250
    .
  26. ^
    PMID 6800852
    .
  27. PMID 6411994
    .
  28. ISBN 978-3-319-52210-4. Archived
    from the original on 28 October 2021. Retrieved 17 December 2017.
  29. S2CID 260086614
    .
  30. ISBN 978-0-08-058368-6. Archived
    from the original on 11 February 2022. Retrieved 17 December 2017.
  31. ^
    PMID 24825748
    .
  32. ^
    ISBN 978-1-4757-2085-3. Archived
    from the original on 12 March 2017. Retrieved 17 December 2017.
  33. ^
    ISBN 978-94-011-4439-1. Archived
    from the original on 12 March 2017. Retrieved 17 December 2017.
  34. ^ "Drugs@FDA: FDA Approved Drug Products". United States Food and Drug Administration. Archived from the original on 16 November 2016. Retrieved 17 December 2017.
  35. ^
    ISBN 978-1-85317-422-3. Archived
    from the original on 8 February 2021. Retrieved 25 December 2017.
  36. ISBN 978-3-11-085367-4
    .
  37. S2CID 24680327
    .
  38. PMID 19591988
    .

Further reading

External links
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