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| Trade names | Suprefact, others |
| Other names | 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) |
| AHFS/Drugs.com | Micromedex Detailed Consumer Information |
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| Routes of administration | Nasal spray,subcutaneous injection,subcutaneous implant[1][2] |
| Drug class | GnRH analogue;GnRH agonist;Antigonadotropin |
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| Pharmacokinetic data | |
| Bioavailability | Oral: ineffective[1] Intranasal: 2.5–3.3%[3] Subcutaneous: 70%[1] |
| Protein binding | 15%[1] |
| Metabolism | Liver,kidneys,gastrointestinal tract (pyroglutamyl peptidase,chymotrypsin-like endopeptidase)[1] |
| Metabolites | Buserelin (1–5)[4] |
| Eliminationhalf-life | Intravenous: 50–80 min[5] Subcutaneous: 80 min[5] Intranasal: 1–2 hours[5] |
| Excretion | Urine,bile[3][5] |
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| ECHA InfoCard | 100.055.493 |
| Chemical and physical data | |
| Formula | C60H86N16O13 |
| Molar mass | 1239.447 g·mol−1 |
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Buserelin, sold under the brand nameSuprefact among others, is amedication which is used primarily in the treatment ofprostate cancer andendometriosis.[3][1][2] It is also used for other indications such as the treatment ofpremenopausalbreast cancer,uterine fibroids, andearly puberty, inassisted reproduction forfemale infertility, and as a part oftransgender hormone therapy.[6][3][7] In addition, buserelin is used inveterinary medicine.[8] The medication is typically used as anasal spray three times per day, but is also available for use as asolution orimplant forinjection into fat.[1][2]
Side effects of buserelin are related tosex hormonedeprivation and includesymptoms oflow testosterone levels andlow estrogen levels such ashot flashes,sexual dysfunction,vaginal atrophy, andosteoporosis.[3][1] Buserelin is agonadotropin-releasing hormone agonist (GnRH agonist) and works by preventing theproduction ofsex hormones by thegonads.[3][1] It can lower sex hormone levels by about 95% in both sexes.[9][10][11] Buserelin is apeptide and ananalogue ofGnRHTooltip gonadotropin-releasing hormone.[12]
Buserelin was first patented in 1974 and approved for medical use in 1985.[13] It is not available in theUnited States, but is marketed widely elsewhere in the world, including in theUnited Kingdom,Canada, and many other countries.[14][8][15] The medication is one of only two medically used GnRH analogues that are available as nasal sprays, the other beingnafarelin.[16] Buserelin is available as ageneric medication.[17][18]
Buserelin is approved for the treatment ofhormone-responsive cancers includingprostate cancer andpremenopausalbreast cancer,sex hormone-dependentuterine diseases includingendometrial hyperplasia,endometriosis, anduterine fibroids, and inassisted reproduction forfemale infertility.[6][3] It is also usedoff-label for the treatment ofprecocious puberty, as apuberty blocker intransgender children, and as a component oftransgender hormone therapy.[3][7] Inovulation induction, buserelin is used forpituitary suppression as anadjunct togonadotropin administration.[19] It has also been assessed as a nasal spray for use as ahormonal contraceptive in women, with a 96%anovulation rate.[3]
For prostate cancer, the dosage of buserelin bysubcutaneous 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.[20][21] If buserelin is used as anasal 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.[21][20] For endometriosis, buserelin is used specifically as a nasal spray and the dosage is the same as that used for prostate cancer.[20] These dosages of buserelin for both subcutaneous injection and nasal spray have been found to decreasetestosterone levels to near-castrate levels in men with prostate cancer, although suppression was more complete with subcutaneous injection presumably due to suboptimalabsorption withintranasal administration.[22]
Buserelin is available in the form of a 1 mg/mLsolution for use as anasal spray orsubcutaneous injection once every 8 hours (three times per day) and as 6.3 mg and 9.45 mgimplants for subcutaneous injection once every two and three months, respectively.[1][2][23][24]
Contraindications of buserelin include the following:[1][2]
During the initial phase of the therapy, before GnRH receptors have been significantlydownregulated,testosterone levels are increased.[3][1] This can lead to transienttumor activation withbone pain (in patients withcancermetastases) andurinary retention.[3][1] Side effects that occur later during the treatment are mainly due tolow sex hormone levels and include reducedlibido,erectile dysfunction,hot flashes,vaginal dryness,vaginal atrophy,menorrhagia,osteoporosis,depression,asthenia,emotional lability,headache,dizziness, and application site reactions.[3][1]
Buserelin appears to be safe in the event of anoverdose.[1][2]
Buserelin is a GnRH agonist, or anagonist of theGnRH receptor.[3][1] It is asuperagonist of the GnRH receptor withpotency for induction ofluteinizing hormone (LH) andfollicle-stimulating hormone (FSH)secretion of about 20 to 170 times that of GnRH itself.[3][1] By activating the GnRH receptor in thepituitary gland, buserelin induces the secretion of LH and FSH from thegonadotrophs of theanterior pituitary, which travel to thegonads through thebloodstream and activate gonadalsex hormoneproduction as well as stimulatespermatogenesis in men andinduce ovulation in women.[3][1]
With chronic administration of buserelin however, the GnRH receptor becomesdesensitized and completely stops responding both to buserelin and toendogenous 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 aloss of LH and FSH secretion from the anterior pituitary and a consequentshutdown of gonadal sex hormone production, markedlydiminished orabolished spermatogenesis in men, andanovulation in women.[3][1]
In men, approximately 95% of circulating testosterone is produced by thetestes, with the remaining 5% being derived from theadrenal glands.[9] In accordance, GnRH analogues like buserelin can reduce testosterone levels by about 95% in men.[9][22] Sex hormone levels, including those ofestradiol andprogesterone, 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 theluteal phase approximately 10–20 ng/mL); the resulting levels are equivalent to those inpostmenopausal 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]
Buserelin is ineffective viaoral administration due tofirst-pass metabolism in thegastrointestinal tract.[1] Itsbioavailability is 2.5 to 3.3% byintranasal administration and 70% bysubcutaneous injection.[1] Theplasma protein binding of buserelin is approximately 15%.[1] Themetabolism of buserelin occurs in theliver,kidneys, and gastrointestinal tract and is mediated bypeptidases, specificallypyroglutamyl peptidase andchymotrypsin-like endopeptidase.[1] Theelimination half-life of buserelin regardless ofroute of administration is about 72 to 80 minutes.[1] Buserelin and itsmetabolites areeliminated inurine andbile, with approximately 50% of buserelinexcreted in urine unchanged.[1][5]
Buserelin is aGnRH analogue, or asyntheticanalogue of GnRH.[3][1] It is anonapeptide and is also known as [D-Ser(tBu)6,des-Gly-NH210]GnRH ethylamide or asD-Ser(tBu)6EA10-GnRH.[3][1][28] Buserelin is marketed for medical use in both itsfree base (buserelin) andacetatesalt (buserelin acetate) forms.[8]
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]
Buserelin is thegeneric name of the drug and itsINNTooltip International Nonproprietary Name andBANTooltip British Approved Name, whilebuserelin acetate is itsUSANTooltip United States Adopted Name,BANMTooltip British Approved Name, andJANTooltip Japanese Accepted Name,buséréline is itsDCFTooltip Dénomination Commune Française, andbuserelina is itsDCITTooltip Denominazione Comune Italiana.[32][8][33][14] While under development byHoechst AG, buserelin was also known asHOE-766.[32][8][33][14]
Buserelin is marketed bySanofi-Aventis primarily under the brand names Suprefact, Suprefact Depot, and Suprecur.[8][14] It is also available under a number of other brand names including Bigonist, Bucel, Buserecur, Fuset, Metrelef, Profact, Profact Depot, Supremon, and Zerelin.[8][14] CinnaFact is a generic version of the medication that is produced byCinnaGen.[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]
Buserelin is marketed in theUnited Kingdom,Ireland, otherEuropean countries,Canada,New Zealand, andSouth Africa, as well as inLatin America,Asia, and elsewhere in the world.[8][14][15] It is not available in theUnited States orAustralia.[8][14][34]
Thesteroidal antiandrogencyproterone 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 witholigoasthenozoospermia andhypogonadotropic hypogonadism.[37][38]
