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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/06 03:26:24」(JST)

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Histrelin acetate is a nonapeptide analog of gonadotropin-releasing hormone (GnRH) with added potency.^[1] When present in the bloodstream, it acts on particular cells of the pituitary gland called gonadotropes. Histrelin stimulates these cells to release luteinizing hormone and follicle-stimulating hormone. Thus it is considered a gonadotropin-releasing hormone agonist or GnRH agonist.

Histrelin is marketed by Endo Pharmaceuticals under the brand names Vantas and Supprelin LA.

Medical uses

Histrelin is used to treat hormone-sensitive cancers of the prostate in men and uterine fibroids in women. In addition, histrelin has been proven to be highly effective in treating central precocious puberty in children.^[2]^[3]

It is available as a daily intramuscular injection.

Histrelin is also available in a 12-month subcutaneous implant (Vantas) for the palliative treatment of advanced prostate cancer (since 2005 in the US, and since Jan 2010 in the UK^[4]).

A 12-month subcutaneous implant (Supprelin LA) for central precocious puberty (CPP) was approved on May 3, 2007 by the U.S. Food and Drug Administration.

Histrelin is also part of the primary care protocol in transgender children/youth, and is used in suppressing cis-sex puberty, until the patient is ready to begin cross-sex hormonal therapy.^[5]

Adverse effects

Side effects are mainly due to low testosterone levels and include headache, hot flashes, reduced libido, and erectile dysfunction.^[6]

Pharmacology

In a process known as downregulation, daily stimulation of pituitary gonadotropes causes them to become desensitized to the effects of histrelin. As a consequence, levels of LH and FSH fall after a short period of time. From that point forward, as long as histrelin is administered, the levels of LH and FSH in the blood remain low.^[7]^[8]

This prolonged lowering of LH and FSH levels is the rationale for therapy using GnRH agonists. Since LH and FSH stimulate the gonads to produce estrogens and androgens in females and males respectively, histrelin can effectively be used to decrease the sex steroids in the blood of patients.

References

^ Histrelin acetate (Vantas) - New Drug Bulletins
^ Histrelin consumer information
^ Eugster, Erica A.; William Clarke; et al. (2007). "Efficacy and Safety of Histrelin Subdermal Implant in Children with Central Precocious Puberty: A Multicenter Trial". J Clin Endocrinol Metab 92 (5): 1697–1704. doi:10.1210/jc.2006-2479. PMID 17327379. Retrieved 2007-10-17.
^ Daily Mail 6 April 2010, p48 "Implant ends the misery of prostate jabs"
^ "Primary Care Protocol for Transgender Patient Care: Hormone Administration". transhealth.ucsf.edu. Retrieved 2015-09-29.
^ Drugs.com: Histrelin monograph
^ Mutschler, Ernst; Schäfer-Korting, Monika (2001). Arzneimittelwirkungen (in German) (8 ed.). Stuttgart: Wissenschaftliche Verlagsgesellschaft. pp. 372–3. ISBN 3-8047-1763-2.
^ Wuttke, W; Jarry, H; Feleder, C; Moguilevsky, J; Leonhardt, S; Seong, J. Y.; Kim, K (1996). "The neurochemistry of the GnRH pulse generator". Acta neurobiologiae experimentalis 56 (3): 707–13. PMID 8917899.

External links

Central Precocious Puberty

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 思春期早発症の治療 treatment of precocious puberty
2. 去勢感受性転移性前立腺癌の初期療法 initial therapy for castration sensitive metastatic prostate cancer

English Journal

Long-Term Continuous Suppression With Once-Yearly Histrelin Subcutaneous Implants for the Treatment of Central Precocious Puberty: A Final Report of a Phase 3 Multicenter Trial.

Silverman LA1, Neely EK1, Kletter GB1, Lewis K1, Chitra S1, Terleckyj O1, Eugster EA1.
The Journal of clinical endocrinology and metabolism.J Clin Endocrinol Metab.2015 Jun;100(6):2354-63. doi: 10.1210/jc.2014-3031. Epub 2015 Mar 24.
CONTEXT AND OBJECTIVE: The histrelin implant has proven to be an effective method of delivering GnRH analog (GnRHa) therapy to children with central precocious puberty (CPP), yet there are limited data available regarding hormonal suppression and auxological changes during an extended course of ther
PMID 25803268

Histrelin for central precocious puberty-a single surgeon experience.

Rosati S1, Maarouf R1, Brown K2, Poppe M2, Parrish D1, Haynes J1, Lanning D3.
The Journal of surgical research.J Surg Res.2015 Mar 30. pii: S0022-4804(15)00330-3. doi: 10.1016/j.jss.2015.03.071. [Epub ahead of print]
BACKGROUND: The most common cause of precocious puberty is idiopathic central precocious puberty (CPP), which is usually treated with monthly injections. An alternative treatment of precious puberty is a subcutaneous implant that contains histrelin acetate, which is continuously released for more th
PMID 25899147

Toward oral delivery of biopharmaceuticals: an assessment of the gastrointestinal stability of 17 peptide drugs.

Wang J1, Yadav V, Smart AL, Tajiri S, Basit AW.
Molecular pharmaceutics.Mol Pharm.2015 Mar 2;12(3):966-73. doi: 10.1021/mp500809f. Epub 2015 Feb 10.
A major barrier to successful oral delivery of peptide and protein molecules is their inherent instability in the lumen of the gastrointestinal tract. The aim of this study was to determine the stability of 17 disparate peptide drugs (insulin, calcitonin, glucagon, secretin, somatostatin, desmopress
PMID 25612507

Related Pictures

These highlights do not include all the information needed to use VANTAS® safely and DailyMed - VANTAS- histrelin acetate implant Vantas implant Drug information on Uses, Side Effects, Interactions, and User Reviews Journal Onkologie | News Druckansicht VANTAS® (histrelin implant) Sell Histrelin Acetate(raw powder)-cosmetic peptide Supprelin LA - FDA prescribing information, side effects and uses

★リンクテーブル★

リンク元	「ヒストレリン」
拡張検索	「histrelin acetate」

「ヒストレリン」

Histrelin
Systematic (IUPAC) name
	5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-1-benzyl-D-histidyl-L-leucyl-N5-(diaminomethylene)-L-ornithyl-N-ethyl-L-prolinamide
Clinical data
AHFS/Drugs.com	monograph
MedlinePlus	a601146
Pregnancy; category	US: X (Contraindicated); ;
Routes of; administration	Subcutaneous implant
Legal status
Legal status	US: ℞-only;
Pharmacokinetic data
Bioavailability	92%
Protein binding	70%
Metabolism	Hepatic
Biological half-life	4.0 hours
Excretion	Undetermined
Identifiers
CAS Number	76712-82-8
ATC code	L02AE05 (WHO)
PubChem	CID 25077993
IUPHAR/BPS	3884
ChemSpider	10482012
UNII	H50H3S3W74
KEGG	D02369
ChEMBL	CHEMBL1201255
Chemical data
Formula	C66H86N18O12
Molar mass	1323.5 g/mol
	SMILES CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(=N)N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC2=CN(C=N2)CC3=CC=CC=C3)NC(=O)[C@H](CC4=CC=C(C=C4)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC5=CNC6=CC=CC=C65)NC(=O)[C@H](CC7=CNC=N7)NC(=O)[C@@H]8CCC(=O)N8 ;
	InChI InChI=1S/C66H86N18O12/c1-4-70-64(95)55-17-11-25-84(55)65(96)48(16-10-24-71-66(67)68)76-58(89)49(26-38(2)3)77-62(93)53(30-43-34-83(37-74-43)33-40-12-6-5-7-13-40)81-59(90)50(27-39-18-20-44(86)21-19-39)78-63(94)54(35-85)82-60(91)51(28-41-31-72-46-15-9-8-14-45(41)46)79-61(92)52(29-42-32-69-36-73-42)80-57(88)47-22-23-56(87)75-47/h5-9,12-15,18-21,31-32,34,36-38,47-55,72,85-86H,4,10-11,16-17,22-30,33,35H2,1-3H3,(H,69,73)(H,70,95)(H,75,87)(H,76,89)(H,77,93)(H,78,94)(H,79,92)(H,80,88)(H,81,90)(H,82,91)(H4,67,68,71)/t47-,48-,49-,50-,51-,52-,53+,54-,55-/m0/s1 ; Key:HHXHVIJIIXKSOE-QILQGKCVSA-N ;
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