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Thomson Walt

เข้าร่วมเมื่อ 15 มกราคม 2559
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Thomson Walt (คุย | ส่วนร่วม)
การแก้ไข 10,278 ครั้ง
Thomson Walt (คุย | ส่วนร่วม)
การแก้ไข 10,278 ครั้ง
บรรทัด 175:
 
Later syntheses have included an "[[atom economy|atom-economical]]" method starting from [[D-Mannitol|<small>D</small>-mannitol]], developed by Indian pharmaceutical company [[Dr. Reddy's Laboratories|Dr. Reddy's]] and reported in 1999,<ref>{{cite journal |vauthors=Lohray BB, Baskaran S, Rao BS, Reddy BY, Rao IN |title=A short synthesis of oxazolidinone derivatives linezolid and eperezolid: A new class of antibacterials |journal=[[Tetrahedron Letters]] |volume=40 |issue=26 |pages=4855–6 |date=June 1999 |doi=10.1016/S0040-4039(99)00893-X}}</ref> and a route starting from (''S'')-glyceraldehyde acetonide (prepared from [[vitamin C]]), developed by a team of researchers from [[Hunan Normal University]] in [[Changsha]], [[Hunan]], China.<ref name=Xu/> On June 25, 2008, during the 12th Annual Green Chemistry and Engineering Conference in New York, Pfizer reported the development of their "second-generation" synthesis of linezolid: a [[convergent synthesis|convergent]], [[green chemistry|green]] synthesis starting from (''S'')-[[epichlorohydrin]], with higher yield and a 56% reduction in total waste.<ref>Perrault WR, Keeler JB, Snyder WC, ''et al.'' (June 25, 2008). [http://acs.confex.com/acs/green08/techprogram/P52019.HTM "Convergent green synthesis of linezolid (Zyvox)"] {{webarchive|url=https://web.archive.org/web/20110728022612/http://acs.confex.com/acs/green08/techprogram/P52019.HTM |date=2011-07-28 }}, in ''12th Annual Green Chemistry and Engineering Conference'', June 24–26, 2008, New York, NY. Retrieved on 2009-06-08.</ref>
==การดื้อยา==
Acquired resistance to linezolid was reported as early as 1999, in two patients with severe, multidrug-resistant ''[[Enterococcus faecium]]'' infection who received the drug through a [[expanded access|compassionate use]] program.<ref name=DrugTherPerspect>{{cite journal |title=Linezolid: First of a New Drug Class for Gram-Positive Infections |journal=Drugs & Therapy Perspectives |volume=17 |issue=9 |pages=1–6 |year=2001 |url=http://www.medscape.com/viewarticle/406493 |author=[No authors listed] |doi=10.2165/00042310-200117090-00001 |deadurl=no |archiveurl=https://web.archive.org/web/20130521043752/http://www.medscape.com/viewarticle/406493 |archivedate=2013-05-21 |df= }}<!--not indexed in MEDLINE--> Free full text with registration at [[Medscape]].</ref> Linezolid-resistant ''[[Staphylococcus aureus]]'' was first isolated in 2001.<ref>{{cite journal |vauthors=Tsiodras S, Gold HS, Sakoulas G, etal |title=Linezolid resistance in a clinical isolate of ''Staphylococcus aureus'' |journal=[[Lancet (journal)|The Lancet]] |volume=358 |issue=9277 |pages=207–8 |date=July 2001 |pmid=11476839 |doi=10.1016/S0140-6736(01)05410-1 |issn=0140-6736}}</ref>
 
In the United States, resistance to linezolid has been monitored and tracked since 2004 through a program named LEADER, which ({{as of|2007|lc=on}}) was conducted in 60 medical institutions throughout the country. Resistance has remained stable and extremely low—less than one-half of one percent of [[wikt:isolate|isolate]]s overall, and less than one-tenth of one percent of ''S. aureus'' samples.<ref name=autogenerated1>{{cite journal |vauthors=Jones RN, Ross JE, Castanheira M, Mendes RE |title=United States resistance surveillance results for linezolid (LEADER Program for 2007) |journal=Diagnostic Microbiology and Infectious Disease |volume=62 |issue=4 |pages=416–26 |date=December 2008 |pmid=19022153 |doi=10.1016/j.diagmicrobio.2008.10.010 |issn=0732-8893}}</ref> A similar, worldwide program—the "Zyvox Annual Appraisal of Potency and Spectrum Study", or ZAAPS—has been conducted since 2002. {{As of|2007}}, overall resistance to linezolid in 23 countries was less than 0.2%, and nonexistent among streptococci. Resistance was only found in Brazil, China, Ireland, and Italy, among [[Staphylococcus#Coagulase-negative|coagulase-negative staphylococci]] (0.28% of samples resistant), enterococci (0.11%), and ''S. aureus'' (0.03%).<ref name=ZAAPS2007>{{cite journal |vauthors=Jones RN, Kohno S, Ono Y, Ross JE, Yanagihara K |title=ZAAPS International Surveillance Program (2007) for linezolid resistance: results from 5591 Gram-positive clinical isolates in 23 countries |journal=Diagnostic Microbiology and Infectious Disease |volume=64 |issue=2 |pages=191–201 |date=June 2009 |pmid=19500528 |doi=10.1016/j.diagmicrobio.2009.03.001 |issn=0732-8893}}</ref> In the United Kingdom and Ireland, no resistance was found in staphylococci collected from [[bacteremia]] cases between 2001 and 2006,<ref>{{cite journal |vauthors=Hope R, Livermore DM, Brick G, Lillie M, Reynolds R |title=Non-susceptibility trends among staphylococci from bacteraemias in the UK and Ireland, 2001–06 |journal=Journal of Antimicrobial Chemotherapy |volume=62 |issue=Suppl 2 |pages=ii65–74 |date=November 2008 |pmid=18819981 |doi=10.1093/jac/dkn353 |url=http://jac.oxfordjournals.org/content/62/suppl_2/ii65.full.pdf |issn=0305-7453}}</ref> although resistance in enterococci has been reported.<ref>{{cite journal |vauthors=Auckland C, Teare L, Cooke F, etal |title=Linezolid-resistant enterococci: report of the first isolates in the United Kingdom |journal=Journal of Antimicrobial Chemotherapy |volume=50 |issue=5 |pages=743–6 |date=November 2002 |pmid=12407134 |url=http://jac.oxfordjournals.org/content/50/5/743.full.pdf |doi=10.1093/jac/dkf246 |issn=0305-7453}}</ref> Some authors have predicted that resistance in ''E. faecium'' will increase if linezolid use continues at current levels or increases.<ref name=Scheetz/> Nevertheless, linezolid continues to be an important antimicrobial agent with near-complete activity (0.05% resistance).<ref name=Bialvaei/>
 
===กลไก===
The ''intrinsic'' resistance of most Gram-negative bacteria to linezolid is due to the activity of [[efflux (microbiology)|efflux pumps]], which [[active transport|actively]] "pump" linezolid out of the cell faster than it can accumulate.<ref name=Barbachyn/><ref>{{cite journal |vauthors=Schumacher A, Trittler R, Bohnert JA, Kümmerer K, Pagès JM, Kern WV |title=Intracellular accumulation of linezolid in ''Escherichia coli'', ''Citrobacter freundii'' and ''Enterobacter aerogenes'': role of enhanced efflux pump activity and inactivation |journal=Journal of Antimicrobial Chemotherapy |volume=59 |issue=6 |pages=1261–4 |date=June 2007 |pmid=16971414 |doi=10.1093/jac/dkl380 |issn=0305-7453 |url=http://jac.oxfordjournals.org/content/59/6/1261.full.pdf }}</ref>
 
Gram-positive bacteria usually develop resistance to linezolid as the result of a [[point mutation]] known as ''G2576T'', in which a [[guanine]] base is replaced with [[thymine]] in [[base pair]] 2576 of the genes coding for 23S ribosomal RNA.<ref name=Saager>{{cite journal |vauthors=Saager B, Rohde H, Timmerbeil BS, etal |title=Molecular characterisation of linezolid resistance in two vancomycin-resistant (VanB) ''Enterococcus faecium'' isolates using Pyrosequencing |journal=European Journal of Clinical Microbiology & Infectious Diseases |volume=27 |issue=9 |pages=873–8 |date=September 2008 |pmid=18421487 |doi=10.1007/s10096-008-0514-6 |issn=0934-9723}}</ref><ref name=Besier>{{cite journal |vauthors=Besier S, Ludwig A, Zander J, Brade V, Wichelhaus TA |title=Linezolid Resistance in Staphylococcus aureus: Gene Dosage Effect, Stability, Fitness Costs, and Cross-Resistances |journal=Antimicrobial Agents and Chemotherapy |volume=52 |issue=4 |pages=1570–2 |date=April 2008 |pmid=18212098 |pmc=2292563 |doi=10.1128/AAC.01098-07 |issn=0066-4804 |url=http://aac.asm.org/cgi/reprint/52/4/1570.pdf }}</ref> This is the most common mechanism of resistance in staphylococci, and the only one known to date in isolates of ''E. faecium''.<ref name=Scheetz>{{cite journal |vauthors=Scheetz MH, Knechtel SA, Malczynski M, Postelnick MJ, Qi C |title=Increasing Incidence of Linezolid-Intermediate or -Resistant, Vancomycin-Resistant Enterococcus faecium Strains Parallels Increasing Linezolid Consumption |journal=Antimicrobial Agents and Chemotherapy |volume=52 |issue=6 |pages=2256–9 |date=June 2008 |pmid=18391028 |pmc=2415807 |doi=10.1128/AAC.00070-08 |issn=0066-4804 |url=http://aac.asm.org/cgi/reprint/52/6/2256.pdf }}</ref> Other mechanisms have been identified in ''[[Streptococcus pneumoniae]]'' (including mutations in an RNA [[methyltransferase]] that methylates G2445 of the 23S rRNA and mutations causing increased [[gene expression|expression]] of [[ATP-binding cassette transporter|ABC transporter]] genes)<ref name=Feng2009>{{cite journal |vauthors=Feng J, Lupien A, Gingras H, etal |title=Genome sequencing of linezolid-resistant Streptococcus pneumoniae mutants reveals novel mechanisms of resistance |journal=Genome Research |volume=19 |issue=7 |pages=1214–23 |date=May 2009 |pmid=19351617 |doi=10.1101/gr.089342.108 |issn=1088-9051 |pmc=2704432}}</ref> and in ''[[Staphylococcus epidermidis]]''.<ref>{{cite journal |vauthors=Lincopan N, de Almeida LM, Elmor de Araújo MR, Mamizuka EM |title=Linezolid resistance in ''Staphylococcus epidermidis'' associated with a G2603T mutation in the 23S rRNA gene |journal=International Journal of Antimicrobial Agents |volume= 34|issue= 3|pages= 281–2|date=April 2009 |pmid=19376688 |doi=10.1016/j.ijantimicag.2009.02.023 |issn=0924-8579}}</ref><ref>{{cite journal |vauthors=Liakopoulos A, Neocleous C, Klapsa D, etal |title=A T2504A mutation in the 23S rRNA gene responsible for high-level resistance to linezolid of ''Staphylococcus epidermidis'' |journal=Journal of Antimicrobial Chemotherapy |volume= 64|issue=1 |pages= 206–7|date=July 2009 |pmid=19429927 |doi=10.1093/jac/dkp167 |issn=0305-7453}}</ref>
==ประวัติและการค้นพบ==
The [[2-Oxazolidone|oxazolidinone]]s have been known as [[monoamine oxidase inhibitor]]s since the late 1950s. Their antimicrobial properties were discovered by researchers at [[DuPont|E.I. duPont de Nemours]] in the 1970s.<ref name=Brickner>{{cite journal |author=Brickner SJ |title=Oxazolidinone antibacterial agents |journal=[[Current Pharmaceutical Design]] |year=1996 |volume=2 |issue=2 |pages=175–94 |url=https://books.google.com/?id=_HFitfA4OcUC&pg=PA175&lpg=PA175}} Detailed review of the discovery and development of the whole oxazolidinone class, including information on [[chemical synthesis|synthesis]] and [[structure-activity relationship]]s.</ref> In 1978, DuPont [[patent]]ed a series of oxazolidinone derivatives as being effective in the treatment of [[bacteria]]l and [[fungus|fungal]] [[plant pathology|plant disease]]s, and in 1984, another patent described their usefulness in treating bacterial infections in [[mammal]]s.<ref name=Moellering>{{cite journal |author=Moellering RC |title=Linezolid: the first oxazolidinone antimicrobial |journal=[[Annals of Internal Medicine]] |volume=138 |issue=2 |pages=135–42 |date=January 2003 |pmid=12529096 |url=http://www.annals.org/cgi/reprint/138/2/135.pdf |issn=0003-4819 |doi=10.7326/0003-4819-138-2-200301210-00015 |deadurl=no |archiveurl=https://web.archive.org/web/20060225164745/http://www.annals.org/cgi/reprint/138/2/135.pdf |archivedate=2006-02-25 |df= }}</ref><ref name=Brickner/> In 1987, DuPont scientists presented a detailed description of the oxazolidinones as a new class of antibiotics with a novel [[mechanism of action]].<ref name=Brickner/><ref name=Slee>{{cite journal |vauthors=Slee AM, Wuonola MA, McRipley RJ, etal |title=Oxazolidinones, a new class of synthetic antibacterial agents: in vitro and in vivo activities of DuP 105 and DuP 721 |journal=[[Antimicrobial Agents and Chemotherapy]] |volume=31 |issue=11 |pages=1791–7 |date=November 1987 |pmid=3435127 |pmc=175041 |url=http://aac.asm.org/cgi/reprint/31/11/1791.pdf |issn=0066-4804 |doi=10.1128/AAC.31.11.1791 |deadurl=no |archiveurl=https://web.archive.org/web/20110611221908/http://aac.asm.org/cgi/reprint/31/11/1791.pdf |archivedate=2011-06-11 |df= }}</ref> Early compounds were found to produce [[hepatotoxicity|liver toxicity]], however, and [[drug development|development]] was discontinued.<ref name=Livermore>{{cite journal |author=Livermore DM |title=Quinupristin/dalfopristin and linezolid: where, when, which and whether to use? |journal=Journal of Antimicrobial Chemotherapy |volume=46 |issue=3 |pages=347–50 |date=September 2000 |pmid=10980159 |url=http://jac.oxfordjournals.org/content/46/3/347.full.pdf |doi=10.1093/jac/46.3.347 |issn=0305-7453}}</ref>
 
[[Pharmacia|Pharmacia &]] [[Upjohn]] (now part of Pfizer) started its own oxazolidinone research program in the 1990s. Studies of the compounds' [[structure-activity relationship|structure–activity relationship]]s led to the development of several subclasses of oxazolidinone derivatives, with varying safety profiles and antimicrobial activity. Two compounds were considered drug candidates: [[eperezolid]] (codenamed ''PNU-100592'') and linezolid (''PNU-100766'').<ref name=Barbachyn>{{cite journal |vauthors=Barbachyn MR, Ford CW |title=Oxazolidinone structure-activity relationships leading to linezolid |journal=[[Angewandte Chemie|Angewandte Chemie International Edition in English]] |volume=42 |issue=18 |pages=2010–23 |date=May 2003 |pmid=12746812 |doi=10.1002/anie.200200528 |issn=1433-7851}}</ref><ref name=French/> In the preclinical stages of development, they were similar in safety and antibacterial activity, so they were taken to [[Phase I trial|Phase I]] [[clinical trial]]s to identify any difference in [[pharmacokinetics]].<ref name=Livermore/><ref name=Ford>{{cite journal |vauthors=Ford CW, Zurenko GE, Barbachyn MR |title=The discovery of linezolid, the first oxazolidinone antibacterial agent |journal=Current Drug Targets&nbsp;– Infectious Disorders |volume=1 |issue=2 |pages=181–99 |date=August 2001 |pmid=12455414 |doi=10.2174/1568005014606099 |issn=1568-0053}}</ref> Linezolid was found to have a pharmacokinetic advantage—requiring only twice-daily dosage, while eperezolid needed to be given three times a day to achieve similar exposure—and therefore proceeded to further trials.<ref name=Barbachyn/> The [[Food and Drug Administration (United States)|U.S. Food and Drug Administration]] (FDA) approved linezolid on April 18, 2000.<ref>{{cite web |url=http://www.fda.gov/cder/foi/nda/2000/21130_Zyvox.htm |archiveurl=https://web.archive.org/web/20080110042651/http://www.fda.gov/cder/foi/nda/2000/21130_Zyvox.htm |archivedate=2008-01-10 |title=Drug Approval Package: Zyvox |date=November 20, 2001 |publisher=FDA [[Center for Drug Evaluation and Research]] |accessdate=2009-01-17}} Comprehensive review of the FDA approval process. Includes detailed reviews of the chemistry and pharmacology of linezolid, correspondence between the FDA and Pharmacia & Upjohn, and administrative documents.</ref> Approval followed in Brazil (June 2000),<ref>{{cite web|author=ANVISA |url=http://www.anvisa.gov.br/legis/resol/2000/474_00re.htm |title=Resolução nº 474, de 5 de junho de 2000 |trans-title=Resolution number 474, of June 5, 2000 |language=Portuguese |date=June 5, 2000 |publisher=[[National Health Surveillance Agency]] |accessdate=2009-05-19 |deadurl=yes |archiveurl=https://web.archive.org/web/20110719081421/http://www.anvisa.gov.br/legis/resol/2000/474_00re.htm |archivedate=July 19, 2011 |df= }}</ref> the United Kingdom (January 2001),<ref name=SPC/><ref name=French/> Japan and Canada (April 2001),<ref>{{cite journal |vauthors=Irinoda K, Nomura S, Hashimoto M |title=[Antimicrobial and clinical effect of linezolid (Zyvox), new class of synthetic antibacterial drug] |language=Japanese |journal=Nippon Yakurigaku Zasshi |volume=120 |issue=4 |pages=245–52 |date=October 2002 |pmid=12425150 |issn=0015-5691 |doi=10.1254/fpj.120.245}}</ref><ref name=CanadaApproval>{{cite press release |url=http://www.docguide.com/news/content.nsf/news/917912FCF5C34DCA85256A46006E24B0 |title=Canada Approves Marketing Of Zyvoxam (Linezolid) For Gram Positive Infections |date=May 8, 2001 |accessdate=2009-05-18 |deadurl=no |archiveurl=https://web.archive.org/web/20080828012714/http://www.docguide.com/news/content.nsf/news/917912FCF5C34DCA85256A46006E24B0 |archivedate=August 28, 2008 |df= }}</ref><ref>{{cite journal |vauthors=Karlowsky JA, Kelly LJ, Critchley IA, Jones ME, Thornsberry C, Sahm DF |title=Determining Linezolid's Baseline In Vitro Activity in Canada Using Gram-Positive Clinical Isolates Collected prior to Its National Release |journal=Antimicrobial Agents and Chemotherapy |volume=46 |issue=6 |pages=1989–92 |date=June 2002 |pmid=12019122 |pmc=127260 |doi=10.1128/AAC.46.6.1989-1992.2002 |issn=0066-4804 |url=http://aac.asm.org/cgi/reprint/46/6/1989.pdf |deadurl=no |archiveurl=https://web.archive.org/web/20110929102627/http://aac.asm.org/cgi/reprint/46/6/1989.pdf |archivedate=2011-09-29 |df= }}</ref> Europe (throughout 2001),<ref>{{cite press release|url=http://www2.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=/www/story/07-25-2001/0001540814&EDATE= |title=Pharmacia Corporation Reports 17% Increase In Second-Quarter Earnings-Per-Share Driven By 61% Increase In Pharmaceutical Earnings |publisher=Pharmacia Corporation |date=July 25, 2001 |accessdate=2009-05-19 |deadurl=yes |archiveurl=https://web.archive.org/web/20120509230639/http://www2.prnewswire.com/cgi-bin/stories.pl?ACCT=104&STORY=%2Fwww%2Fstory%2F07-25-2001%2F0001540814&EDATE= |archivedate=May 9, 2012 |df= }}</ref> and other countries in Latin America and Asia.<ref name=CanadaApproval/>
 
{{As of|2009}}, linezolid is the only oxazolidinone antibiotic available.<ref name=Livermore2009>{{cite journal |vauthors=Livermore DM, Mushtaq S, Warner M, Woodford N |title=Activity of oxazolidinone TR-700 against linezolid-susceptible and -resistant staphylococci and enterococci |journal=Journal of Antimicrobial Chemotherapy |volume=63 |issue=4 |pages=713–5 |date=April 2009 |pmid=19164418 |doi=10.1093/jac/dkp002 |issn=0305-7453}}</ref> Other members of this class have entered development, such as [[posizolid]] (AZD2563),<ref>{{cite journal |vauthors=Howe RA, Wootton M, Noel AR, Bowker KE, Walsh TR, MacGowan AP |title=Activity of AZD2563, a Novel Oxazolidinone, against Staphylococcus aureus Strains with Reduced Susceptibility to Vancomycin or Linezolid |journal=Antimicrobial Agents and Chemotherapy |volume=47 |issue=11 |pages=3651–2 |date=November 2003 |pmid=14576139 |pmc=253812 |doi=10.1128/AAC.47.11.3651-3652.2003 |issn=0066-4804 |url=http://aac.asm.org/cgi/reprint/47/11/3651.pdf |deadurl=no |archiveurl=https://web.archive.org/web/20110929080102/http://aac.asm.org/cgi/reprint/47/11/3651.pdf |archivedate=2011-09-29 |df= }}</ref> [[ranbezolid]] (RBx 7644),<ref>{{cite journal |vauthors=Kalia V, Miglani R, Purnapatre KP, etal |title=Mode of Action of Ranbezolid against Staphylococci and Structural Modeling Studies of Its Interaction with Ribosomes |journal=Antimicrobial Agents and Chemotherapy |volume=53 |issue=4 |pages=1427–33 |date=April 2009 |pmid=19075051 |doi=10.1128/AAC.00887-08 |issn=0066-4804 |pmc=2663096}}</ref> [[torezolid]] (TR-701),<ref name=Livermore2009/><ref>{{cite press release |url=http://www.medicalnewstoday.com/articles/136728.php |title=Trius Completes Enrollment In Phase 2 Clinical Trial Evaluating Torezolid (TR-701) In Patients With Complicated Skin And Skin Structure Infections |date=2009-01-27 |accessdate=2009-05-17 |deadurl=no |archiveurl=https://web.archive.org/web/20090214082932/http://www.medicalnewstoday.com/articles/136728.php |archivedate=2009-02-14 |df= }}</ref> and [[radezolid]] (RX-1741).<ref>{{cite web |url=http://www.rib-x.com/pipeline/rx_1741 |title= Rx 1741 |publisher=Rib-X Pharmaceuticals |year=2009 |accessdate=2009-05-17 |archiveurl=https://web.archive.org/web/20090226201337/http://www.rib-x.com/pipeline/rx_1741 <!--Added by H3llBot--> |archivedate=2009-02-26}}</ref>
==ประเด็นที่เกี่ยวเนื่องกับสังคมและวัฒนธรรม==
 
===เศรษฐกิจ===
{{further|Pharmacoeconomics|Disease burden}}
 
Linezolid was quite expensive in 2009; a course of treatment may cost one or two thousand U.S. dollars for the drug alone,<ref name=Lexi-Comp/> not to mention other costs (such as those associated with hospital stay). With the medication becoming generic the price has decreased such that in United States the wholesale cost of a course of treatment as of 2016 is about US$137.90.<ref name=Medi2016/> In India as of 2015 a month of linezolid, as would be used to treat tuberculosis cost about US$60.<ref name=WHO2015Use/>
 
However, because intravenous linezolid may be switched to an oral formulation (tablets or oral solution) without jeopardizing efficacy, people may be discharged from hospital relatively early and continue treatment at home, whereas home treatment with injectable antibiotics may be impractical.<ref name=Grau2008/> Reducing the [[length of stay|length of hospital stay]] reduces the overall cost of treatment, even though linezolid may have a higher acquisition cost—that is, it may be more expensive—than comparable antibiotics.
 
Studies have been conducted in several countries with different [[health care system]] models to assess the [[cost-effectiveness analysis#CEA in pharmacoeconomics|cost-effectiveness]] of linezolid compared to glycopeptides such as vancomycin or teicoplanin. In most countries, linezolid was more cost-effective than comparable antibiotics for the treatment of hospital-acquired pneumonia and complicated skin and skin structure infections, either due to higher cure and survival rates or lower overall treatment costs.<ref name=Grau2008/>
 
In 2009, Pfizer paid $2.3&nbsp;billion and entered a corporate integrity agreement to settle charges that it had misbranded and illegally promoted four drugs, and caused false claims to be submitted to government healthcare programs for uses that had not been approved by the United States Food and Drug Administration.<ref>{{cite news |url=http://news.bbc.co.uk/2/hi/business/8234533.stm |title=Pfizer agrees record fraud fine |publisher=BBC News |date=September 2, 2009 |accessdate=2009-09-12 |deadurl=no |archiveurl=https://web.archive.org/web/20090908011344/http://news.bbc.co.uk/2/hi/business/8234533.stm |archivedate=September 8, 2009 |df= }}</ref> $1.3&nbsp;billion was paid to settle criminal charges of illegally marketing the anti-inflammatory [[valdecoxib]], while $1&nbsp;billion was paid in civil fines regarding illegal marketing of three other drugs, including Zyvox.<ref>{{cite news |url=https://www.nytimes.com/2009/09/03/business/03health.html |title=Pfizer pays $2.3 billion to settle marketing case |last=Harris |first=Gardiner |date=September 2, 2009 |work=[[The New York Times]] |accessdate=2009-09-12 |deadurl=no |archiveurl=https://web.archive.org/web/20110822013720/http://www.nytimes.com/2009/09/03/business/03health.html |archivedate=August 22, 2011 |df= }}</ref>
 
===ชื่อการค้า===
Linezolid is marketed by [[Pfizer]] under the trade names Zyvox (in the United States, United Kingdom, Australia, and several other countries), Zyvoxid (in Europe), and Zyvoxam (in Canada and Mexico). Generics are also available, such as linezomentin (in Egypt, by Arabcomed), Lenzomore (in India, by Morepen), Linospan (in India, by [[Cipla]]), Nezocin (in Pakistan, by [[Brookes]]), voxazoldin (in Egypt, by Rotabiogen), Lizomed (in India, as a dry syrup by Aglowmed), and Linzolid (in Bangladesh, by [[Incepta]]).
 
==อ้างอิง==
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