Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/11/18 23:09:56」(JST)

wiki en

Bumetanide (trade names Bumex or Burinex) is a loop diuretic of the sulfamyl category to treat heart failure. It is often used in people in whom high doses of furosemide are ineffective. It is marketed by Hoffmann-La Roche. The main difference between the two substances is in bioavailability and pharmacodynamic potency. Furosemide is incompletely absorbed in the intestine (60%), and there is substantial inter- and intraindividual differences in bioavailability (range 10-90%). Bumetanide is almost completely absorbed (80%), and the absorption is not altered when it is taken with food. It is said to be a more predictable diuretic, meaning that the predictable absorption is reflected in a more predictable effect.^[1]

Bumetanide is 40 times more potent than furosemide (for patients with normal renal function).^[1]

In the brain, bumetanide blocks the NKCC1 cation-chloride co-transporter, and thus decreases internal chloride concentration in neurons. In turn, this concentration change makes the action of GABA more hyperpolarizing, which may be useful for treatment of neonatal seizures, that quite often are not responsive to traditional GABA-targeted treatment, such as barbiturates. Bumetanide is therefore currently under evaluation as a prospective antiepileptic drug.^[2]

Abuse

On October 24, 2008, ESPN reported a number of NFL players were being suspended under the steroid policy as a result of taking bumetanide. The drug is often used for weight loss, but also to mask other drugs or steroids by helping to dilute the contents of the user's urine, yielding a lower concentration of filtered substances which may then go undetected.

Bumetanide was an undisclosed active ingredient in the over the counter weight loss supplement StarCaps. StarCaps was pulled off the market after the presence of the undisclosed ingredient was discovered by the Food and Drug Administration.

Synthesis

Bumetanide, 3-butylamino-4-phenoxy-5-sulfamoylbenzoic acid, is synthesized from 4-chlorobenzoic acid. In the first stage of synthesis, it undergoes sulfonylchlorination by chlorosulfonic acid, forming 4-chloro-3-chlorosulfonylbenzoic acid, which is further nitrated with nitric acid to 4-chloro-3-chlorosulfonyl-5-nitrobenzoic acid. Reacting this with ammonia gives 5-aminosulfonyl-4-chloro-3-nitrobenzoic acid, which when reacted with sodium phenolate is transformed into 5-amino-sulfonyl-3-nitro-5-phenoxybenzoid acid. Reduction of the nitro group in this product by hydrogen using a palladium on carbon catalyst gives 3-amino-5-aminosulfonyl- 5-phenoxybenzoic acid. Finally, reacting this with butyl alcohol in the presence of sulfuric acid gives the desired bumetanide.

Source:

F.P. Werner, Ger. Pat. DE 1964503 (1970).
F.P. Werner, Ger. Pat. DE 1964504 (1970).
P. Feit, U.S. Pat. U.S. Patent 33,806,534 (1974).
P.W. Feit, U.S. Pat. U.S. Patent 3,634,583 (1972).
Feit, P. W. (1971). "Aminobenzoic acid diuretics. 2. 4-Substituted-3-amino-5-sulfamoylbenzoic acid derivatives". Journal of Medicinal Chemistry 14 (5): 432–9. doi:10.1021/jm00287a014. PMID 5117690. edit

References

^ ^a ^b Brunton, Laurence; Lazo, John S.; Parker, Keith L., eds. (2006). Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. pp. 749–753. ISBN 0-07-142280-3.
^ Löscher W, Puskarjov M, Kaila K (June 2013). "Cation-chloride cotransporters NKCC1 and KCC2 as potential targets for novel antiepileptic and antiepileptogenic treatments". Neuropharmacology 69: 62–74. doi:10.1016/j.neuropharm.2012.05.045. PMID 22705273.

External links

Bumex [1] (FDA)
Bumetanide (patient information)

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. ループ利尿剤：最大有効量および主な副作用 loop diuretics maximum effective dose and major side effects
2. 心不全患者における利尿剤の使用 use of diuretics in patients with heart failure
3. 成人における難治性浮腫の治療 treatment of refractory edema in adults
4. 利尿剤の作用機序 mechanism of action of diuretics
5. 高血圧治療におけるサイアザイド系利尿剤とループ利尿剤の比較 thiazides versus loop diuretics in treatment of hypertension

English Journal

Bumetanide continuous-infusion dosing in critically ill pediatric patients.

Bulkley CF, Johnson PN, Henry E, Harrison D, Lewis TV, Miller JL.
American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists.Am J Health Syst Pharm.2012 Sep 1;69(17):1458-61.
PMID 22899737

Intracellular Na+, K+ and Cl- activities in Acheta domesticus Malpighian tubules and the response to a diuretic kinin neuropeptide.

Coast GM.SourceBirkbeck, University of London, London WC1E 7HX, UK.
The Journal of experimental biology.J Exp Biol.2012 Aug 15;215(Pt 16):2774-85.
The mechanism of primary urine production and the activity of a diuretic kinin, Achdo-KII, were investigated in Malpighian tubules of Acheta domesticus by measuring intracellular Na(+), K(+) and Cl(-) activities, basolateral membrane voltage (V(b)), fluid secretion and transepithelial ion transport.
PMID 22837449

Japanese Journal

Functional Analysis of Human Sodium-Phosphate Transporter 4 (NPT4/SLC17A3) Polymorphisms

Jutabha Promsuk,Anzai Naohiko,Kimura Toru,Taniguchi Atsuo,Urano Wako,Yamanaka Hisashi,Endou Hitoshi,Sakurai Hiroyuki
Journal of Pharmacological Sciences 115(2), 249-253, 2011
… NPT4 variants carrying SNP V257F, G279R, or P378L exhibited reduced transport of [14C]para-aminohippurate, [3H]bumetanide, [3H]estrone sulfate, and [14C]urate, when each variant clone was expressed in the plasma membrane of oocytes. …
NAID 130000439950

Ribosomal protein L3 mediated the transport of digoxin in Xenopus laevis oocyte

KOBAYASHI Yasuna,KAWAKAMI Kanako,OHBAYASHI Masayuki,KOHYAMA Noriko,YAMAMOTO Toshinori
Journal of toxicological sciences 35(6), 827-834, 2010-12-01
… The maximum velocity of the transport of [3H]digoxin via RPL3 produced at physiological pH. However, we did not observe RPL3-mediated transport of several organic solutes such as [14C]androstenedione, [3H]dexamethasone, [3H]dehydroepiandrosterone sulfate, [3H]L-tryptophan, [14C]L-ascorbic acid, [14C]α-ketoglutarate, [14C]glutarate, [3H]methotrexate, [3H]bumetanide, [3H]probenecid, [14C]salicylic acid, [14C]theophylline and [3H]valproate. …
NAID 10026962974

Related Pictures

★リンクテーブル★

リンク元	「利尿薬」「ブメタニド」

「利尿薬」

Bumetanide
Systematic (IUPAC) name
	3-butylamino-4-phenoxy-5-sulfamoyl-benzoic acid
Clinical data
Trade names	Bumex
AHFS/Drugs.com	monograph
MedlinePlus	a684051
Pregnancy cat.	AU: B3; US: C;
Legal status	AU: Prescription Only (S4); UK: POM; US: ℞-only;
Routes	oral, intravenous, intramuscular
Pharmacokinetic data
Bioavailability	almost complete (~80%)
Protein binding	97%
Metabolism	hepatic
Half-life	~0.8 hours
Excretion	renal
Identifiers
CAS number	28395-03-1
ATC code	C03CA02
PubChem	CID 2471
DrugBank	DB00887
ChemSpider	2377
UNII	0Y2S3XUQ5H
KEGG	D00247
ChEBI	CHEBI:3213
ChEMBL	CHEMBL1072
Chemical data
Formula	C17H20N2O5S
Mol. mass	364.417 g/mol
	SMILES O=S(=O)(c2cc(cc(NCCCC)c2Oc1ccccc1)C(=O)O)N;
	InChI InChI=1S/C17H20N2O5S/c1-2-3-9-19-14-10-12(17(20)21)11-15(25(18,22)23)16(14)24-13-7-5-4-6-8-13/h4-8,10-11,19H,2-3,9H2,1H3,(H,20,21)(H2,18,22,23) ; Key:MAEIEVLCKWDQJH-UHFFFAOYSA-N ;
(what is this?) (verify)