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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/01/31 10:37:06」(JST)

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Grepafloxacin hydrochloride (trade name Raxar, Glaxo Wellcome) was an oral broad-spectrum fluoroquinolone antibacterial agent used to treat bacterial infections. Grepafloxacin was withdrawn world wide from markets owing to its side effect of lengthening the QT interval on the electrocardiogram, leading to cardiac events and sudden death.^[1]

GlaxoSmithKline marketed Raxar at doses of 200 milligrams, 400 milligrams and 600 milligrams. Records filed with the U.S. Food and Drug Administration (FDA) showed that Raxar was cited as a suspect in the reported deaths of 13 patients.^{[citation needed]} There were four deaths associated with patients who took Raxar in 600-milligram doses within the clinical trials submitted with the New Drug Application (NDA) in 1997.^{[citation needed]} The package insert approved by the FDA stated that "there were no deaths or permanent disabilities" among those who took Raxar in 400-milligram doses. It was the FDA’s position that none of the noted fatalities "was shown to be attributable to Raxar." On Oct. 27, 1999, GlaxoSmithKline removed Raxar from clinical use citing to the fact that Raxar's effect on "QT interval prolongation" was unacceptably risky. ^[2]^{[unreliable source?]}

Other drugs within this class (i.e. sparfloxacin, moxifloxacin, levofloxacin, gatifloxacin, gemifloxacin) have also been associated with QT interval prolongation, resulting in sudden death of the patient.^[3]^{[dead link]}^{[medical citation needed]}

References[edit]

^ Sprandel, KA.; Rodvold, KA. (2003). "Safety and tolerability of fluoroquinolones.". Clin Cornerstone. Suppl 3: S29–36. PMID 14992418.
^ http://www.mail-archive.com/sustainablelorgbiofuel@sustainablelists.org/msg54680.html
^ Fluoroquinolones and QT prolongation research continues Prolongation of the QT interval is associated with potentially life-threatening ventricular tachyarrhythmias such as torsades de pointes. by Kimberly Madewell, PharmD http://www.infectiousdiseasenews.com/article/33493.aspx

UpToDate Contents

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1. フルオロキノロン類 fluoroquinolones
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English Journal

Fluoroquinolones, the Cornerstone of Treatment of Drug-Resistant Tuberculosis: A Pharmacokinetic and Pharmacodynamic Approach.

Pranger AD, Alffenaar JW, Aarnoutse RE.SourceDepartment of Hospital and Clinical pharmacy, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. j.w.c.alffenaar@apoth.umcg.nl.
Current pharmaceutical design.Curr Pharm Des.2011 Aug 12. [Epub ahead of print]
Fluoroquinolones (FQs) are important drugs to treat drug-resistant tuberculosis. In this review we integrated pharmacokinetic properties (PK) and microbiological susceptibility against M. tuberculosis and eventually evaluated the pharmcodynamic (PD) properties, as well as the influence of co-adminis
PMID 21834759

Ventricular rate adaptation: A novel, rapid, cellular-based in-vitro assay to identify proarrhythmic and torsadogenic compounds.

Green JR, Diaz GJ, Limberis JT, Houseman KA, Su Z, Martin RL, Cox BF, Kantor S, Gintant GA.AbstractINTRODUCTION: Delayed cardiac repolarization is an established risk factor for proarrhythmia and Torsades-de-Pointes (TdeP) that is typically measured in vitro during slow, regular stimulation. We have developed an alternative, novel, and rapid cellular-based approach for predicting drug-induced proarrhythmia that detects changes in electrical refractoriness based on mechanical responses (measured optically) during increasingly rapid trains of stimulation interspersed with pauses (mimicking the clinically observed short-long-short (SLS) stimulation sequence associated with the TdeP initiation).
Journal of pharmacological and toxicological methods.J Pharmacol Toxicol Methods.2011 Jul-Aug;64(1):68-73. Epub 2011 Apr 2.
INTRODUCTION: Delayed cardiac repolarization is an established risk factor for proarrhythmia and Torsades-de-Pointes (TdeP) that is typically measured in vitro during slow, regular stimulation. We have developed an alternative, novel, and rapid cellular-based approach for predicting drug-induced pro
PMID 21440075

Japanese Journal

Carrier-Mediated Uptake of Grepafloxacin, a Fluoroquinolone Antibiotic, by the Isolated Rat Lung Cells

SASABE Hiroyuki,KATO Yukio,SUZUKI Takashi,ITOSE Minoru,MIYAMOTO Gohachiro,SUGIYAMA Yuichi
Drug metabolism and pharmacokinetics 20(6), 491-495, 2005-12-27
NAID 10016901081

新キノロン薬グレパフロキサシンのヒト好中球機能との相互作用におけるp38MAPK活性化の関与 : Uptake ならびに Priming 能を指標に

丹羽雅之,堀田功一,金森豊,廣田雅生,小澤修,藤本貞毅
炎症・再生 : 日本炎症・再生医学会雑誌 = Inflammation and regeneration 25(6), 501-506, 2005-11-25
… Grepafloxacin is an asymmetric fluoroquinolone derivative, which possesses high tissue penetrability as well as strong, broad-spectrum antimicrobial activities. … Human neutrophils actively internalize fluoroquinolones, especially grepafloxacin, and grepafloxacin induces a priming effect on neutrophil respiratory burst produced by fMLP. …
NAID 10026499389

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★リンクテーブル★

リンク元	「グレパフロキサシン」
拡張検索	「grepafloxacin hydrochloride hydrate」「grepafloxacin hydrochloride」

「グレパフロキサシン」

Grepafloxacin
Systematic (IUPAC) name
	(RS)-1-cyclopropyl-6-fluoro-5-methyl-7-(3-methylpiperazin-1-yl)- 4-oxo-quinoline- 3-carboxylic acid
Clinical data
AHFS/Drugs.com	Multum Consumer Information
Legal status	?
Pharmacokinetic data
Protein binding	50%
Identifiers
CAS number	119914-60-2
ATC code	J01MA11
PubChem	CID 72474
DrugBank	DB00365
ChemSpider	65391
UNII	L1M1U2HC31
KEGG	C11368
ChEMBL	CHEMBL583
Chemical data
Formula	C19H22FN3O3
Mol. mass	359.395 g/mol
	SMILES O=C(O)\C2=C\N(c1cc(c(F)c(c1C2=O)C)N3CC(NCC3)C)C4CC4;
	InChI InChI=1S/C19H22FN3O3/c1-10-8-22(6-5-21-10)15-7-14-16(11(2)17(15)20)18(24)13(19(25)26)9-23(14)12-3-4-12/h7,9-10,12,21H,3-6,8H2,1-2H3,(H,25,26) ; Key:AIJTTZAVMXIJGM-UHFFFAOYSA-N ;
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