Rifampicin


Rifampicin, also known as rifampin, is an antibiotic used to treat several types of bacterial infections2 This includes tuberculosis, leprosy, and Legionnaire's disease It is almost always used along with other antibiotics, except when given to prevent Haemophilus influenzae type b and meningococcal disease in people who have been exposed to those bacteria Before treating a person for a long period of time, measurements of liver enzymes and blood counts are recommended Rifampicin may be given either by mouth or intravenously2

Common side effects include nausea, vomiting, diarrhea, and loss of appetite It often turns urine, sweat, and tears a red or orange color Liver problems or allergic reactions may occur It is part of the recommended treatment of active tuberculosis during pregnancy, even though its safety in pregnancy is not known Rifampicin is of the rifamycin group of antibiotics It works by stopping the production of RNA by bacteria2

Rifampicin was discovered in 1965, marketed in Italy in 1968, and approved in the United States in 1971345 It is on the World Health Organization's List of Essential Medicines, the most effective and safe medicines needed in a health system6 It is available as a generic medication2 The wholesale cost in the developing world is about 390 USD a month7 In the United States it is expensive, with a month of treatment being about 120 USD28 Rifampicin is made by the soil bacterium Amycolatopsis rifamycinica5

Contents

  • 1 Medical uses
    • 11 Mycobacteria
    • 12 Other bacteria and protozoans
    • 13 Viruses
    • 14 Pathogen susceptibility
  • 2 Adverse effects
  • 3 Chemical structure
  • 4 Interactions
  • 5 Mechanism of action
    • 51 Mechanism of resistance
    • 52 Resistance in tuberculosis
  • 6 Pharmacokinetics
  • 7 Use in biotechnology
  • 8 History
  • 9 Names
  • 10 References
  • 11 External links

Medical usesedit

Rifampicin powder

Mycobacteriaedit

Rifampicin is used for the treatment of tuberculosis in combination with other antibiotics, such as pyrazinamide, isoniazid, and ethambutol9 For the treatment of tuberculosis, it is administered daily for at least 6 months10 Combination therapy is utilized both to prevent the development of resistance and to shorten the length of treatment11 Resistance of Mycobacterium tuberculosis to rifampicin develops quickly when it is used without another antibiotic, with laboratory estimates of resistance rates from 10−7 to 10−10 per tuberculosis bacteria per generation1213

Rifampicin can be used alone in patients with latent tuberculosis infections to prevent or prolong the development of active disease because only small numbers of bacteria are present A Cochrane review found no difference in efficacy between a three to four month regimen of rifampicin and a six-month regimen of isoniazid for preventing active tuberculosis in patients not infected with HIV, and patients who received rifampicin had a lower rate of hepatotoxicity14 However, the quality of the evidence was judged to be low14 A shorter two-month course of rifampicin and pyrazinamide had previously been recommended, but is no longer due to high rates of hepatotoxicity15

Rifampicin should be taken on an empty stomach with a glass of water It is generally taken either at least one hour before meals or two hours after meals16

Rifampicin is also used to treat non-tuberculous mycobacterial infections including leprosy Hansen's disease and Mycobacterium kansasii17

With multidrug therapy used as the standard treatment of Hansen's disease, rifampicin is always used in combination with dapsone and clofazimine to avoid causing drug resistance

Other bacteria and protozoansedit

Rifampicin is sometimes used in the treatment of methicillin-resistant Staphylococcus aureus MRSA in combination with fusidic acid, including in difficult-to-treat infections such as osteomyelitis and prosthetic joint infections18 It is also used as preventive treatment against Neisseria meningitidis meningococcal infections Rifampicin is also recommended as an alternative treatment for infections by the tick-borne pathogens Borrelia burgdorferi and Anaplasma phagocytophilum when treatment with doxycycline is contraindicated, such as in pregnant women or in patients with a history of allergy to tetracycline antibiotics1920

It is also sometimes used to treat infections by Listeria species, Neisseria gonorrhoeae, Haemophilus influenzae, and Legionella pneumophila For these nonstandard indications, antimicrobial susceptibility testing should be done if possible before starting rifampicin therapy

The Enterobacteriaceae, Acinetobacter species, and Pseudomonas species are intrinsically resistant to rifampicin

It has been used with amphotericin B in largely unsuccessful attempts to treat primary amoebic meningoencephalitis caused by Naegleria fowleri

Rifampicin can be used as monotherapy for a few days as prophylaxis against meningitis, but resistance develops quickly during long-term treatment of active infections, so the drug is always used against active infections in combination with other antibiotics21

Rifampicin is relatively ineffective against spirochetes, which has led to its use as a selective agent capable of isolating them in materials being cultured in laboratories22

Virusesedit

Rifampicin has some effectiveness against vaccinia virus2324

Pathogen susceptibilityedit

The following is information about minimum inhibitory concentrations of rifampicin for several medically significant pathogens:

  • Mycobacterium tuberculosis — 0002 – 64 µg/mL
  • Mycobacterium bovis — 0125 µg/mL
  • Stapylococcus aureus methicillin resistant — ≤0006–256 µg/mL25
  • Chlamydia pneumoniae — 0005 µg/mL26

Adverse effectsedit

The most serious adverse effect is hepatotoxicity, and patients receiving it often undergo baseline and frequent liver function tests to detect early liver damage

The more common side effects include fever, gastrointestinal disturbances, rashes, and immunological reactions Taking rifampicin usually causes certain bodily fluids, such as urine, sweat, and tears, to become orange-red in color, a benign side effect that nonetheless can be frightening if it is not expected This may also be used to monitor effective absorption of the drug if drug color is not seen in the urine, the patient may wish to move the drug dose farther in time from food or milk intake The discolorization of sweat and tears is not directly noticeable, but sweat may stain light clothing orange, and tears may permanently stain soft contact lenses Since rifampicin may be excreted in breast milk, breast feeding should be avoided while it is being taken

Other adverse effects include:

  • Liver toxicity — hepatitis, liver failure in severe cases
  • Respiratory — breathlessness
  • Cutaneous — flushing, pruritus, rash, hyperpigmentation,27 redness and watering of eyes
  • Abdominal — nausea, vomiting, abdominal cramps, diarrhea
  • Flu-like symptoms — chills, fever, headache, arthralgia, and malaise Rifampicin has good penetration into the brain, and this may directly explain some malaise and dysphoria in a minority of users
  • Allergic reaction — rashes, itching, swelling of the tongue or throat, severe dizziness, and trouble breathing28

Chemical structureedit

Rifampicin is a polyketide belonging to the chemical class of compounds termed ansamycins, so named because of their heterocyclic structure containing a napthoquinone core spanned by an aliphatic ansa chain The napthoquinonic chromophore is what gives rifampicin its characteristic red-orange crystalline color

The critical functional groups of rifampicin in its inhibitory binding of bacterial RNA polymerase are the four critical hydroxyl groups of the ansa bridge and the napthol ring, which form hydrogen bonds with amino acid residues on the protein29

Rifampicin is the 3-4-methyl-1-piperazinyl-iminomethyl derivative of rifamycin SV30

Interactionsedit

Rifampicin is the most powerful known inducer of the hepatic cytochrome P450 enzyme system, including isoenzymes CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP3A4, CYP3A5, and CYP3A731 It increases metabolism of many drugs and as a consequence, can make them less effective, or even ineffective, by decreasing their levels32 For instance, patients undergoing long-term anticoagulation therapy with warfarin have to increase their dosage of warfarin and have their clotting time checked frequently because failure to do so could lead to inadequate anticoagulation, resulting in serious consequences of thromboembolism33

Rifampicin can reduce the efficacy of birth control pills or other hormonal contraception by its induction of the cytochrome P450 system, to the extent that unintended pregnancies have occurred in women who use oral contraceptives and took rifampicin even for very short courses for example, as prophylaxis against exposure to bacterial meningitis

Other interactions include decreased levels and less effectiveness of antiretroviral agents, everolimus, atorvastatin, rosiglitazone, pioglitazone, celecoxib, clarithromycin, caspofungin, voriconazole, and lorazepam34

Rifampicin is antagonistic to the microbiologic effects of the antibiotics gentamicin and amikacin

Mechanism of actionedit

Binding of rifampicin in the active site of RNA polymerase Mutation of amino acids shown in red are involved in resistance to the antibiotic

Rifampicin inhibits bacterial DNA-dependent RNA synthesis by inhibiting bacterial DNA-dependent RNA polymerase35

Crystal structure data and biochemical data suggest that rifampicin binds to the pocket of the RNA polymerase β subunit within the DNA/RNA channel, but away from the active site29 The inhibitor prevents RNA synthesis by physically blocking elongation, and thus preventing synthesis of host bacterial proteins By this "steric-occlusion" mechanism, rifampicin blocks synthesis of the second or third phosphodiester bond between the nucleotides in the RNA backbone, preventing elongation of the 5' end of the RNA transcript past more than 2 or 3 nucleotides3637

Mechanism of resistanceedit

Resistance to rifampicin arises from mutations that alter residues of the rifampicin binding site on RNA polymerase, resulting in decreased affinity for rifampicin37 Resistance mutations map to the rpoB gene, encoding the beta subunit of RNA polymerase The majority of resistance mutations in E coli are in 3 clusters on rpoB12 Cluster I is amino acids 509 to 533, cluster II is amino acids 563 to 572, and cluster III is amino acid 687

When describing mutations in rpoB in other species, the corresponding amino acid number in E coli is usually used In Mycobacterium tuberculosis, the majority of mutations leading to rifampicin resistance are in cluster I, in a 81bp hotspot core region called RRDR for "rifampcin resistance determining region"38 A change in amino acid 531 from serine to leucine arising from a change in the DNA sequence of TCG to TTG is the most common mutation12 Tuberculosis resistance has also occurred due to mutations in the N-terminal region of rpoB and cluster III12

An alternative mechanism of resistance is through Arr-catalyzed ADP-ribosylation of rifampicin With the assistance of the enzyme Arr produced by the pathogen Mycobacterium smegmatis, ADP-ribose is added to rifampicin at one of its ansa chain hydroxy groups, thereby inactivating the drug39

Resistance in tuberculosisedit

Mycobacterial resistance to rifampicin may occur alone or along with resistance to other first line anti-tubercular drugs Early detection of such multi-drug or extensively drug-resistant tuberculosis is critical in improving patient outcomes by instituting appropriate second-line treatments, and in decreasing transmission of drug-resistant TB40 Traditional methods of detecting resistance involve Mycobacterial culture and drug susceptibility testing, results of which could take up to six weeks Xpert MTB/RIF assay is an automated test that can detect rifampicin resistance, and also diagnose tuberculosis A Cochrane review updated in 2014 concluded that for rifampicin resistance detection, Xpert MTB/RIF was accurate, that is 95% sensitive and 98% specific41

Pharmacokineticsedit

Orally administered rifampicin results in peak plasma concentrations in about two to four hours 4-Aminosalicylic acid another antituberculosis drug significantly reduces absorption of rifampicin,42 and peak concentrations may be lower If these two drugs must be used concurrently, they must be given separately, with an interval of eight to 12 hours between administrations

Rifampicin is easily absorbed from the gastrointestinal tract; its ester functional group is quickly hydrolyzed in bile, and it is catalyzed by a high pH and substrate-specific esterases After about six hours, almost all of the drug is deacetylated Even in this deacetylated form, rifampicin is still a potent antibiotic; however, it can no longer be reabsorbed by the intestines and is eliminated from the body Only about 7% of the administered drug is excreted unchanged in urine, though urinary elimination accounts for only about 30% of the drug excretion About 60% to 65% is excreted through feces

The half-life of rifampicin ranges from 15 to 50 hours, though hepatic impairment significantly increases it Food consumption inhibits its absorption from the GI tract, and the drug is more quickly eliminated When rifampicin is taken with a meal, its peak blood concentration falls by 36% Antacids do not affect its absorption43 The decrease in rifampicin absorption with food is sometimes enough to noticeably affect urine color, which can be used as a marker for whether or not a dose of the drug has been effectively absorbed

Distribution of the drug is high throughout the body, and reaches effective concentrations in many organs and body fluids, including the cerebrospinal fluid Since the substance itself is red, this high distribution is the reason for the orange-red color of the saliva, tears, sweat, urine, and feces About 60% to 90% of the drug is bound to plasma proteins44


Use in biotechnologyedit

Rifampicin inhibits bacterial RNA polymerase, thus it is commonly used to inhibit the synthesis of host bacterial proteins during recombinant protein expression in bacteria RNA encoding for the recombinant gene is usually transcribed from DNA by a viral T7 RNA polymerase, which is not affected by rifampicin

Historyedit

In 1957, a soil sample from a pine forest on the French Riviera was brought for analysis to the Lepetit Pharmaceuticals research lab in Milan, Italy There, a research group headed by Piero Sensi45 and Maria Teresa Timbal discovered a new bacterium This new species produced a new class of molecules with antibiotic activity Because Sensi, Timbal and the researchers were particularly fond of the French crime story Rififi about a jewel heist and rival gangs,46 they decided to call these compounds "rifamycins" After two years of attempts to obtain more stable semisynthetic products, a new molecule with high efficacy and good tolerability was produced in 1965 and was named "rifampicin"3

Rifampicin was first sold in Italy in 1968 and was approved by the FDA in 19713

Namesedit

Rifampicin is the INN and BAN while rifampin is the USAN Rifampicin may be abbreviated R, RMP, RA, RF, or RIF US

Rifampicin is also known as rifaldazine,4748 rofact, and rifampin in the United States, also as rifamycin SV49

Its chemical name is 5,6,9,17,19,21-hexahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-N-4-methyl-1-piperazinylformimidoyl-2,7-epoxypentadeca1,11,13trienimino-naphtho2,1-bfuran-1,112H-dione 21-acetate

Rifampicin is available under many brand names worldwide50

Referencesedit

  1. ^ "Rifampicin CAS 13292-46-1" Santa Cruz Biotechnology Product Block Santa Cruz Biotechnology Retrieved 14 November 2014 
  2. ^ a b c d e "Rifampin" The American Society of Health-System Pharmacists Retrieved Aug 1, 2015 
  3. ^ a b c Sensi, P 1983 "History of the development of rifampin" Reviews of Infectious Diseases 5 Suppl 3: S402–6 JSTOR 4453138 PMID 6635432 doi:101093/clinids/5supplement_3s402 
  4. ^ Oxford Handbook of Infectious Diseases and Microbiology OUP Oxford 2009 p 56 ISBN 978-0-19-103962-1 
  5. ^ a b McHugh, Timothy D 2011 Tuberculosis: diagnosis and treatment Wallingford, Oxfordshire: CAB International p 219 ISBN 978-1-84593-807-9 
  6. ^ "WHO Model List of Essential Medicines 19th List" PDF World Health Organization April 2015 Retrieved 8 December 2016 
  7. ^ "Rifampicin" International Drug Price Indicator Guide Retrieved 24 August 2015 
  8. ^ Hamilton, Richard J 2014 Tarascon pocket pharmacopoeia: 2014 deluxe lab-pocket edition 15 ed Sudbury: Jones & Bartlett Learning p 39 ISBN 978-1-284-05399-9 
  9. ^ "Treatment of tuberculosis: guidelines" World Health Organization 2010 ISBN 978-92-4-154783-3 
  10. ^ Long, James W 1991 Essential Guide to Prescription Drugs 1992 New York: HarperCollins Publishers pp 925–929 ISBN 0-06-273090-8 
  11. ^ Erlich, Henry, W Ford Doolittle, Volker Neuhoff, et al Molecular Biology of Rifamycin New York, NY: MSS Information Corporation, 1973 pp 44-45, 66-75, 124-130
  12. ^ a b c d Goldstein, Beth P "Resistance to rifampicin: a review" The Journal of Antibiotics 67 9: 625–630 doi:101038/ja2014107 
  13. ^ David HL 1970 "Probability Distribution of Drug-Resistant Mutants in Unselected Populations of Mycobacterium tuberculosis" Appl Microbiol 20: 810–4 PMC 377053  PMID 4991927 
  14. ^ a b Sharma, SK; Sharma, A; Kadhiravan, T; Tharyan, P July 5, 2013 "Rifamycins rifampicin, rifabutin and rifapentine compared to isoniazid for preventing tuberculosis in HIV-negative people at risk of active TB" The Cochrane Database of Systematic Reviews 7: CD007545 PMID 23828580 doi:101002/14651858CD007545pub2 CS1 maint: Multiple names: authors list link
  15. ^ "Update: adverse event data and revised American Thoracic Society/CDC recommendations against the use of rifampin and pyrazinamide for treatment of latent tuberculosis infection - United States, 2003" MMWR Morbidity and Mortality Weekly Report 52 31: 735–739 2003-08-08 ISSN 1545-861X PMID 12904741 
  16. ^ "Rifampin oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD" WebMD WebMD Retrieved 13 November 2014 
  17. ^ The Sanford Guide to Antimicrobial Therapy 2015 ISBN 978-1-930808-84-3 
  18. ^ Aboltins CA, Page MA, Buising KL, et al June 2007 "Treatment of staphylococcal prosthetic joint infections with debridement, prosthesis retention and oral rifampicin and fusidic acid" Clinical Microbiology and Infection 13 6: 586–591 PMID 17331125 doi:101111/j1469-0691200701691x 
  19. ^ Wormser, Gary P; Dattwyler, Raymond J; Shapiro, Eugene D; Halperin, John J; Steere, Allen C; Klempner, Mark S; Krause, Peter J; Bakken, Johan S; Strle, Franc; Stanek, Gerold; Bockenstedt, Linda; Fish, Durland; Stephen Dumler, J; Nadelman, Robert B 1 November 2006 "The Clinical Assessment, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: Clinical Practice Guidelines by the Infectious Diseases Society of America" Clinical Infectious Diseases 43 9: 1089–1134 PMID 17029130 doi:101086/508667 CS1 maint: Multiple names: authors list link
  20. ^ Thomas RG, Dumler SJ, Carlyon JA August 2009 "Current management of human granulocytic anaplasmosis, human monocytic ehrlichiosis and Ehrlichia ewingii ehrlichiosis" Expert Reviews in Anti-Infection Therapies 7 6: 709–722 PMC 2739015  PMID 19681699 doi:101586/eri0944 
  21. ^ "Rifampicin" Retrieved August 22, 2014 
  22. ^ Leschine, SB; Canale-Parola, E December 1980 "Rifampin as a Selective Agent for the Isolation of Oral Spirochetes" PDF Journal of Clinical Microbiology 12 6: 792–795 PMC 273700  PMID 7309842 Retrieved 3 March 2016 
  23. ^ Charity JC, Katz E, Moss B March 2007 "Amino acid substitutions at multiple sites within the vaccinia virus D13 scaffold protein confer resistance to rifampicin" Virology 359 1: 227–32 PMC 1817899  PMID 17055024 doi:101016/jvirol200609031 
  24. ^ Sodeik B, Griffiths G, Ericsson M, Moss B, Doms RW February 1994 "Assembly of vaccinia virus: effects of rifampin on the intracellular distribution of viral protein p65" Journal of Virology 68 2: 1103–14 PMC 236549  PMID 8289340 
  25. ^ "Rifampicin Rifampin - The Antimicrobial Index Knowledgebase - TOKU-E" toku-ecom 
  26. ^ Gieffers J, Solbach W, Maass M 1998 "Note: In Vitro Susceptibilities of Chlamydia pneumoniae Strains Recovered from Atherosclerotic Coronary Arteries" Antimicrobial Agents and Chemotherapy 42: 2762–4 PMC 105936  PMID 9756794 
  27. ^ Pugazhenthan Thangaraju; Hosanna Singh; M Punitha; VC Giri; MK Showkath Ali 2015 "Hyperpigmentation, a marker of rifampicin overuse in leprosy patient: An incidental finding" Sudan Med Monitor 10 1: 25–26 doi:104103/1858-5000157506 
  28. ^ "Rifampin oral: Uses, Side Effects, Interactions, Pictures, Warnings & Dosing – WebMD" WebMD WebMD Retrieved 13 November 2014 
  29. ^ a b Campbell, Elizabeth A; Korzheva, Nataliya; Mustaev, Arkady; Murakami, Katsuhiko; Nair, Satish; Goldfarb, Alex; Darst, Seth A March 2001 "Structural Mechanism for Rifampicin Inhibition of Bacterial RNA Polymerase" Cell 104 6: 901–912 PMID 11290327 doi:101016/s0092-86740100286-0 
  30. ^ Bennett, John 2015 Principles and Practice of Infectious Diseases Elsevier Health Sciences p 339 
  31. ^ "Division of Clinical Pharmacology | Indiana University Department of Medicine" Medicineiupuiedu 2011-09-27 Retrieved 2011-11-07 
  32. ^ Collins, R Douglas Atlas of Drug Reactions New York, NY: ChurchillLivingstone, 1985 pp 123
  33. ^ Stockley, Ivan H "Anticoagulant Drug Interactions" Drug Interactions 3rd ed Boston: Blackwell Scientific Publications, 1994 pp 274-275
  34. ^ Riss, J; Cloyd, J; Gates, J; Collins, S August 2008 "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics" Acta Neurologica Scandinavica 118 2: 69–86 PMID 18384456 doi:101111/j1600-0404200801004x 
  35. ^ Calvori, C; Frontali, L; Leoni, L; Tecce, G 1965 "Effect of rifamycin on protein synthesis" Nature 207 995: 417–8 PMID 4957347 doi:101038/207417a0 
  36. ^ Campbell, EA, Korzheva, N, Mustaev, A, Murakami, K, Nair, S, Goldfarb, A, Darst, SA 2001 "Structural mechanism for rifampicin inhibition of bacterial RNA polymerase" Cell 104 6: 901–12 PMID 11290327 doi:101016/S0092-86740100286-0 CS1 maint: Multiple names: authors list link
  37. ^ a b Feklistov, A, Mekler, V, Jiang, Q, Westblade, LF, Irschik, H, Jansen, R, Mustaev, A, Darst, SA, Ebright, RH 2008 "Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center" Proceedings of the National Academy of Sciences of the United States of America 105 39: 14820–5 PMC 2567451  PMID 18787125 doi:101073/pnas0802822105 CS1 maint: Multiple names: authors list link
  38. ^ Pierre-Audiger, C; Gicquel, B "The Contribution of Molecular Biology in Diagnosing Tuberculosis and Detecting Antibiotic Resistance" PDF Molecular TB 
  39. ^ Baysarowich, Jennifer; Koteva, Kalinka; Hughes, Donald W; Ejim, Linda; Griffiths, Emma; Zhang, Kun; Junop, Murray; Wright, Gerard D 2008-03-25 "Rifamycin antibiotic resistance by ADP-ribosylation: Structure and diversity of Arr" Proceedings of the National Academy of Sciences 105 12: 4886–4891 ISSN 0027-8424 PMC 2290778  PMID 18349144 doi:101073/pnas0711939105 
  40. ^ Policy Framework for Implementing New Tuberculosis Diagnostics PDF Geneva: World Health Organization 2011 Retrieved 21 March 2016 
  41. ^ Steingart, KR; Schiller, I; Horne, DJ; Pai, M; Boehme, CC; Dendukuri, N 21 January 2014 "Xpert MTB/RIF assay for pulmonary tuberculosis and rifampicin resistance in adults" The Cochrane Database of Systematic Reviews 1: CD009593 PMC 4470349  PMID 24448973 doi:101002/14651858CD009593pub3 Retrieved 21 March 2016 
  42. ^ G Curci, A Ninni, AD'Aleccio 1969 Atti Tavola Rotonda Rifampicina, Taormina, page 19 Edizioni Rassegna Medica, Lepetit, Milano
  43. ^ "Kinetics of Rifampin taken with food and with antacids" PDF Retrieved 2011-11-07 
  44. ^ Hardman, Joel G, Lee E Limbird, and Alfred G Gilman, eds "Rifampin" The Pharmacological Basis of Therapeutics 10th ed United States of America: The McGraw-Hill Companies, 2001 pp 1277–1279
  45. ^ "Il chimico che salvò molte vite" corriereit 
  46. ^ "When I Use a Word I Mean It" British Medical Journal 1999;3197215:972 9 October Retrieved 2009-07-10 
  47. ^ Moncalvo F, Moreo G 1966 "Ricerche cliniche preliminari sull'impiego di una nuova rifamicina orale rifaldazina nella terapia della tubercolosi polmonare nota preventiva" Giornale Italiano Della Tubercolosi E Delle Malattie Del Torace 20 3: 120–31 PMID 5974175 
  48. ^ "Rifampicin" Chemical Safety Information from Intergovernmental Organizations International Programme on Chemical Safety Retrieved 14 November 2014 
  49. ^ "US Patent 3963705" Patent Google US Patent Office Retrieved 14 November 2014 
  50. ^ Drugscom international listings for Rifampicin Accessed Jan 15 2015

External linksedit

  • PubPK – Rifampicin pharmacokinetics
  • Prescribing Information for RIFADIN by Sanofi-Aventis
  • US National Library of Medicine: Drug Information Portal – Rifampicin
  • PDRnet Concise Monograph – Rifadin


Rifampicin Information about

Rifampicin

Rifampicin
Rifampicin

Rifampicin Information Video


Rifampicin viewing the topic.
Rifampicin what, Rifampicin who, Rifampicin explanation

There are excerpts from wikipedia on this article and video