Linezolid
Systematic (IUPAC) name
N-[[3-(3-fluoro-4-morpholinophenyl)- 2-oxooxazolidin-5-yl]methyl]acetamide
Identifiers
CAS number	165800-03-3
ATC code	J01XX08
PubChem	441401
DrugBank	APRD01073
Chemical data
Formula	C16H20FN3O4
Mol. mass	337.346 g/mol
Pharmacokinetic data
Bioavailability	~100% (oral)
Protein binding	31%
Metabolism	Hepatic 50–70%
Half life	4.2–5.4 hours
Excretion	Renal 80–85%
Therapeutic considerations
Pregnancy cat.	C (Au), C (U.S.) Image File history File links Description: Chemical structure of Linezolid. ... IUPAC nomenclature is a system of naming chemical compounds and of describing the science of chemistry in general. ... CAS registry numbers are unique numerical identifiers for chemical compounds, polymers, biological sequences, mixtures and alloys. ... The Anatomical Therapeutic Chemical Classification System is used for the classification of drugs. ... A section of the Anatomical Therapeutic Chemical Classification System. ... PubChem is a database of chemical molecules. ... The DrugBank database available at the University of Alberta is a unique bioinformatics and cheminformatics resource that combines detailed drug (i. ... A chemical formula is a concise way of expressing information about the atoms that constitute a particular chemical compound. ... For other uses, see Carbon (disambiguation). ... This article is about the chemistry of hydrogen. ... Distinguished from fluorene and fluorone. ... General Name, symbol, number nitrogen, N, 7 Chemical series nonmetals Group, period, block 15, 2, p Appearance colorless gas Standard atomic weight 14. ... General Name, symbol, number oxygen, O, 8 Chemical series nonmetals, chalcogens Group, period, block 16, 2, p Appearance colorless (gas) pale blue (liquid) Standard atomic weight 15. ... The molecular mass (abbreviated Mr) of a substance, formerly also called molecular weight and abbreviated as MW, is the mass of one molecule of that substance, relative to the unified atomic mass unit u (equal to 1/12 the mass of one atom of carbon-12). ... In pharmacology, bioavailability is used to describe the fraction of an administered dose of unchanged drug that reaches the systemic circulation, one of the principal pharmacokinetic properties of drugs. ... A drugs efficacy may be affected by the degree to which it binds to the proteins within blood plasma. ... Drug metabolism is the metabolism of drugs, their biochemical modification or degradation, usually through specialized enzymatic systems. ... The biological half-life of a substance is the time required for half of that substance to be removed from an organism by either a physical or a chemical process. ... The kidneys are important excretory organs in vertebrates. ... The pregnancy category of a pharmaceutical agent is an assessment of the risk of fetal injury due to the pharmaceutical, if it is used as directed by the mother during pregnancy. ... For other uses, see Australia (disambiguation). ... For other uses of terms redirecting here, see US (disambiguation), USA (disambiguation), and United States (disambiguation) Motto In God We Trust(since 1956) (From Many, One; Latin, traditional) Anthem The Star-Spangled Banner Capital Washington, D.C. Largest city New York City National language English (de facto)1 Demonym American...
Legal status	S4 (Au), POM (UK), ℞-only (U.S.) The regulation of therapeutic goods, that is drugs and therapeutic devices, varies by jurisdiction. ...
Routes	IV, oral

Linezolid (INN) (IPA: [lɪnɛˈzəlɪd]) is a synthetic antibiotic, the first of the oxazolidinone class, used for the treatment of infections caused by multi-resistant bacteria including streptococcus and methicillin-resistant Staphylococcus aureus (MRSA). It is marketed under the trade name Zyvox (or Zyvoxid in Europe) (Pfizer). In pharmacology and toxicology, a route of administration is the path by which a drug, fluid, poison or other substance is brought into contact with the body. ... An intravenous drip in a hospital Intravenous therapy or IV therapy is the administration of liquid substances directly into a vein. ... An International Nonproprietary Name (INN) is the official non-proprietary or generic name given to a pharmaceutical substance, as designated by the World Health Organization. ... Articles with similar titles include the NATO phonetic alphabet, which has also informally been called the “International Phonetic Alphabet”. For information on how to read IPA transcriptions of English words, see IPA chart for English. ... Staphylococcus aureus - Antibiotics test plate. ... Oxazolidinones are the last generation of antibiotics used against gram-positive pathogens, including superbugs such as Staphylococcus aureus. ... Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ... Streptococcus is a genus of spherical shaped Gram-positive bacteria, belonging to the phylum Firmicutes[1] and the lactic acid bacteria group. ... MRSA redirects here. ... For other uses, see Europe (disambiguation). ... Pfizer, Incorporated (NYSE: PFE), is a global pharmaceutical company, with headquarters in New York City. ...

It was the first commercially available oxazolidinone antibiotic and is usually reserved for the treatment of serious bacterial infections where older antibiotics have failed due to antibiotic resistance. Conditions such as skin infections or nosocomial pneumonia where methicillin or penicillin resistance is found are indicators for linezolid use. Compared to the older antibiotics it is quite expensive. Oxazolidinones are the last generation of antibiotics used against gram-positive pathogens, including superbugs such as Staphylococcus aureus. ... Phyla Actinobacteria Aquificae Chlamydiae Bacteroidetes/Chlorobi Chloroflexi Chrysiogenetes Cyanobacteria Deferribacteres Deinococcus-Thermus Dictyoglomi Fibrobacteres/Acidobacteria Firmicutes Fusobacteria Gemmatimonadetes Lentisphaerae Nitrospirae Planctomycetes Proteobacteria Spirochaetes Thermodesulfobacteria Thermomicrobia Thermotogae Verrucomicrobia Bacteria (singular: bacterium) are unicellular microorganisms. ... Antibiotic resistance is the ability of a microorganism to withstand the effects of an antibiotic. ... This article is about human pneumonia. ... Methicillin (USAN) or meticillin (INN, BAN) is a narrow spectrum beta-lactam antibiotic. ... For the Japanese rock band, see Penicillin (band). ...

The drug works by inhibiting the initiation of bacterial protein synthesis. Initially there was hope that bacteria would be unable to develop resistance to it. However, in 2001 Staphylococcus aureus was first identified as being resistant to linezolid.^[1] Linezolid is effective against gram-positive pathogens, notably Enterococcus faecium, Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pneumoniae, and Streptococcus pyogenes. It has almost no effect on gram-negative bacteria and is only bacteriostatic against most Enterococcus species. Linezolid also provides some anaerobic coverage. Linezolid has been used to treat tuberculosis.^[2] Binomial name Rosenbach 1884 Staphylococcus aureus , literally Golden Cluster Seed and also known as golden staph, is the most common cause of staph infections. ... Gram-positive bacteria are those that are stained dark blue or violet by gram staining, in contrast to gram-negative bacteria, which are not affected by the stain. ... Enterococcus faecium is a gram positive bacterium in the genus Enterococcus. ... Streptococcus agalactiae is a gram-positive streptococcus characterized by the presence of group B Lancefield antigen. ... Binomial name (Klein 1884) Chester 1901 Streptococcus pneumoniae, or pneumococcus, is a Gram-positive, alpha-hemolytic diplococcus bacterium and a member of the genus Streptococcus. ... Binomial name Rosenbach 1884 Streptococcus pyogenes is a spherical gram-positive bacteria that grows in long chains [1] and is the cause of Group A streptococcal infections. ... Bacteriostatic antibiotics hamper the growth of bacteria by interfering with bacteria protein production, interfering with bacteria DNA production interfering with bacteria cellular metabolism Bacteriostatic antibiotics inhibit growth and repoduction of the bacteria, though do not kill it, while bactericidal antibiotics kill bacteria. ... Species E. faecalis etc. ... The standard short course treatment for tuberculosis (TB) is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, then isoniazid and rifampicin alone for a further four months. ...

The oxazolidinone class was discovered by researchers at E.I. duPont de Nemours and reported in 1987. Upjohn developed linezolid (Upjohn is now part of Pfizer) and Food and Drug Administration (FDA) approval was granted in April of 2000. It is sold in the U.S. under the tradename Zyvox in either tablet form, oral suspension powder, or in an inactive medium for intravenous injection. First signs of resistance was reported in 2001. Year 1987 (MCMLXXXVII) was a common year starting on Thursday (link displays 1987 Gregorian calendar). ... The Upjohn Company was a pharmaceutical manufacturing firm founded in 1886 by Dr. William E. Upjohn in Kalamazoo, Michigan. ... Pfizer Incorporated (NYSE: PFE) is the worlds largest research-based pharmaceutical company[1].[1] The company is based in New York City. ... “FDA” redirects here. ... This article or section needs additional references or sources to improve its verifiability. ... Year 2000 (MM) was a leap year starting on Saturday (link will display full 2000 Gregorian calendar). ...

Mechanism of Action

Linezolid works on the initiation of protein synthesis. It does this by stopping the 30S and 50S subunits of the ribosome from binding together. Linezolid binds on the 23S portion of the 50S subunit close to the peptidyl transferase and chloramphenicol binding sites. This then stops the interaction with the 30S subunit. This is a VERY expensive drug. If it is not covered by your insurance, 28 pills can cost you over $2,000.00! Centuries: 1st century BC - 1st century - 2nd century Decades: 20s BC - 10s BC - 0s - 10s - 20s - 30s - 40s - 50s - 60s - 70s - 80s 30 31 32 33 34 35 36 37 38 39 Sometimes the 30s is used as shorthand for the 1930s, the 1830s, or other such decades in various... Centuries: 1st century BC - 1st century - 2nd century Decades: 0s - 10s - 20s - 30s - 40s - 50s - 60s - 70s - 80s - 90s - 100s 50 51 52 53 54 55 56 57 58 59 Sometimes the 50s is used as shorthand for the 1950s, the 1850s, or other such decades in various centuries Events... Chloramphenicol is a bacteriostatic antibiotic originally derived from the bacterium Streptomyces venezuelae, isolated by David Gottlieb, and introduced into clinical practice in 1949. ...

Dosing

The adult dose of linezolid is 600mg twice daily orally or intravenously for a maximum of 14 days. The dose in children is 10mg/kg orally or intravenously three times a day for a maximum of 14 days.

Linezolid has been used in the treatment of tuberculosis (in combination with other drugs).^[2] The optimal dose for use in tuberculosis is not known. In adults, 600mg daily^[3] or 600mg twice daily^[4] have both been used to good effect. The treatment often needs to be continued for many months and the rate of adverse effects is high.^[3] The lower dose is not associated with a lower rate of adverse effects.^[3] The standard short course treatment for tuberculosis (TB) is isoniazid, rifampicin, pyrazinamide and ethambutol for two months, then isoniazid and rifampicin alone for a further four months. ...

Adverse effects

Side effects include rashes, loss of appetite, diarrhea, nausea, constipation and fever. A small number of patients will incur a severe allergic reaction, or tinnitus, or pseudomembranous colitis. Thrombocytopenia is uncommon in patients who receive linezolid for 14 days or less (the manufacturer's recommendation), but in patients who receive longer courses, or who have renal failure, the rate is much higher.^[5] The anemia and thrombocytopenia caused by linezolid are not prevented by concurrent administration of pyridoxine 125mg daily.^[6] Books on tinnitus Tinnitus (pronounced or ,[1] from the Latin word for ringing[2]) is the perception of sound in the human ear in the absence of corresponding external sound(s). ... Pseudomembranous colitis is an infection of the colon often, but not always, caused by the bacterium Clostridium difficile. ... Thrombocytopenia (or -paenia, or thrombopenia in short) is the presence of relatively few platelets in blood. ... Main article: vitamin B6 Pyridoxine is one of the compounds that can be called vitamin B6, along with Pyridoxal and Pyridoxamine. ...

Linezolid is a weak monoamine oxidase inhibitor (MAOI) and cannot be used with tyramine containing foods or pseudoephedrine. MAOI redirects here. ... In organic chemistry tyramine (4-hydroxy-phenethylamine, para-tyramine, p-tyramine) is a monoamine compound derived from the amino acid tyrosine. ... Pseudoephedrine (commonly abbreviated as PSE) is a sympathomimetic amine commonly used as a decongestant. ...

Linezolid is toxic to mitochondria (probably because of the similarity between mitochondrial and bacterial ribosomes). Signs of mitochondrial toxicity include lactic acidosis and peripheral neuropathy.^[7] Painful sensory neuropathy (PMID: 17766431). In cell biology, a mitochondrion is an organelle found in the cells of most eukaryotes. ... Figure 1: Ribosome structure indicating small subunit (A) and large subunit (B). ... Lactic acidosis is a condition caused by the buildup of lactic acid in the body. ... Peripheral neuropathy is the term for damage to nerves of the peripheral nervous system, which may be caused either by diseases of the nerve or from the side-effects of systemic illness. ...

External links

• http://www.zyvox.com/
• http://www.fda.gov/cder/drug/infopage/linezolid/default.htm

References

1. ^ Tsiodras S, Gold HS, Sakoulas G, et al. Linezolid resistance in a clinical isolate of Staphylococcus aureus. Lancet. 2001 Jul 21;358(9277):207-8.
2. ^ ^{a b} von der Lippea B, Sandvenb P, Brubakk O. (2006). "Efficacy and safety of linezolid in multidrug resistant tuberculosis (MDR-TB)—a report of ten cases". J Infect 52 (2): 92–6. doi:10.1016/j.jinf.2005.04.007. 
3. ^ ^{a b c} Park IN, Hong SB, Oh YM, et al. (2006). "Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis". J Antimicrob Chemother 58 (3): 701–4. PMID 16857689. 
4. ^ Fortun J, Martin-Davila P, Navas E, et al. (2005). "Linezolid for the treatment of multidrug-resistant tuberculosis". J Antimicrob Chemother 56 (1): 180–5. doi:10.1093/jac/dki148. 
5. ^ Lin Y-H, Wu V-C, Tsai I-J, et al.. "High frequency of linezolid-associated thrombocytopenia among patients with renal insufficiency". Int J Antimicrob Agents (4): 345–51. doi:10.1016/j.ijantimicag.2006.04.017. 
6. ^ Plachouras D, Giannitsioti E, Athanassia S, et al. (2006). "No effect of pyridoxine on the incidence of myelosuppression during prolonged linezolid treatment". Clin Infect Dis 43 (9): e89–91. 
7. ^ Soriano A, Miró O, Mensa J. "Mitochondrial Toxicity Associated with Linezolid". N Engl J Med 353 (21): 2305–6.