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an antibacterial drug (trade names Rifadin and Rimactane) used to treat tuberculosis (同)Rifadin, Rimactane

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/17 20:26:18」(JST)

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Rifampicin (INN) /rɪˈfæmpəsɪn/ or rifampin (USAN) is a bactericidal antibiotic drug of the rifamycin group.^[1] It is a semisynthetic compound derived from Amycolatopsis rifamycinica (formerly known as Amycolatopsis mediterranei and Streptomyces mediterranei).^[2] Rifampicin may be abbreviated R, RMP, RA, RF, or RIF (US).

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 Prof. Piero Sensi (1920-) and Dr. Maria Teresa Timbal (1925 - 1969) discovered a new bacterium. This new species appeared immediately of great scientific interest since it was producing 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),^[3] 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 1959 and was named "rifampicin".

Rifampicin is also known as rifaldazine, R/AMP, rofact (in Canada), and rifampin in the United States. There are various types of rifamycins from which this is derived, but the rifampicin form, with a 4-methyl-1-piperazinaminyl group, is by far the most clinically effective.

Rifampicin is an intensely red solid, and the small fraction which reaches body fluids is known for imparting a harmless red-orange color to the urine (and to a lesser extent, also sweat and tears) of users, for a few hours after a dose. Maximal concentrations in the blood are decreased by about a third when the antibiotic is taken with food.^[4]

Indications[edit]

Rifampicin was introduced in 1967,^[5] as a major addition to the cocktail-drug treatment of tuberculosis and inactive meningitis, along with pyrazinamide, isoniazid, ethambutol and streptomycin ("PIERS"). It requires a prescription in North America. It must be administered regularly daily for several months without break; otherwise, the risk of drug-resistant tuberculosis is greatly increased.^[5] In fact, this is the primary reason it is used in tandem with the three aforementioned drugs, particularly isoniazid.^[6] This is also the primary motivation behind directly observed therapy for tuberculosis.

Rifampicin resistance develops quickly during treatment, so monotherapy should not be used to treat these infections — it should be used in combination with other antibiotics.

Rifampicin is also used in the treatment of cholestatic pruritus.^[7]

Mycobacteria[edit]

Rifampicin is typically used to treat Mycobacterium infections, including tuberculosis and Hansen's disease. It can be used to treat BCG-oma, which follows as an uncommon complication of BCG vaccination for tuberculosis.

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

Other bacteria[edit]

Rifampicin is 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 infections.^[8] It is also used in prophylactic therapy against Neisseria meningitidis (meningococcal) infection. Rifampicin is also recommended as an alternative treatment for infections with the tick-borne disease 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 antibiotics.^[9]^[10]

It is also used to treat infection by Listeria species, Neisseria gonorrhoeae, Haemophilus influenzae and Legionella pneumophila. For these nonstandard indications, sensitivity testing should be done (if possible) before starting rifampicin therapy.

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

Further, 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 treatment of active infections, so the drug is always used against active infections in combination with other antibiotics.

Viruses[edit]

Rifampicin has some effectiveness against vaccinia virus.^[11]^[12]

Mechanism of action[edit]

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 polymerase.^[13]

Crystal structure data and biochemical data indicate that rifampicin binds to RNA polymerase at a site adjacent to the RNA polymerase active center and blocks RNA synthesis by physically preventing extension of RNA products beyond a length of 2-3 nucleotides ("steric-occlusion" mechanism).^[14]^[15]

Resistance to rifampicin arises from mutations that alter residues of the rifampicin binding site on RNA polymerase, resulting in decreased affinity for rifampicin.^[15] Resistant mutations map to the rpoB gene, encoding RNA polymerase beta subunit.

Adverse effects[edit]

The most serious adverse effect is related to rifampicin's hepatotoxicity, and patients receiving it often undergo baseline and frequent liver function tests to detect liver damage.

Rifampicin is an effective liver enzyme-inducer, promoting the upregulation of hepatic cytochrome P450 enzymes (such as CYP2C9 and CYP3A4), increasing the rate of metabolism of many other drugs that are cleared by the liver through these enzymes. As a consequence, rifampicin can cause a range of adverse reactions when taken concurrently with other drugs.^[16] For instance, patients undergoing long term anticoagulation therapy with warfarin have to be especially cautious and increase their dosage of warfarin accordingly.^[17] Failure to do so could lead to under-treating with anticoagulation, resulting in serious consequences of thromboembolism.

Upregulation of hepatic metabolism of hormones decreases their levels, and rifampicin can also in similar fashion reduce the efficacy of hormonal contraception, to the extent the unintended pregnancies have been reported among users of oral contraceptives taking rifampicin in even short courses (for example, as prophylaxis against exposure to bacterial meningitis).

The more common unwanted effects include fever, gastrointestinal disturbances, rashes, and immunological reactions.

Taking rifampicin can cause certain bodily fluids, such as urine and tears, to become orange-red in color, a benign side effect which can be frightening if it is not expected and prepared for. This effect 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 discolorizion 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.

Adverse effects include:

Hepatotoxic - hepatitis, liver failure in severe cases
Respiratory - breathlessness
Cutaneous - flushing, pruritus, rash, redness and watering of eyes
Abdominal - nausea, vomiting, abdominal cramps with or without diarrhea
Flu-like symptoms - with chills, fever, headache, arthralgia, and malaise, rifampin has good penetration into the brain, and this may directly explain some malaise and dysphoria in a minority of users.

Pharmacokinetics[edit]

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,^[18] and peak concentrations may not be reached. If these two drugs must be used concurrently (which happens often in treatment of TB), 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 the bile; and it is catalyzed by a high pH and substrate-specific enzymes called esterases. After about six hours, almost all of the drug is deacetylated. Even in this deacetylated form, rifampin is still a potent antibiotic; however, it can no longer be reabsorbed by the intestines and it is subsequently eliminated from the body. Only about 7% of the administered drug will be excreted unchanged through the urine, though urinary elimination accounts for only about 30% of the drug excretion. About 60% to 65% is excreted through the feces.

The half-life of rifampicin ranges from 1.5 to 5.0 hours, though hepatic impairment will significantly increase it. Food consumption, on the other hand, inhibits absorption from the GI tract, and the drug is more quickly eliminated. When rifampicin is taken with a meal, peak blood concentration falls by 36%. Antacids do not affect absorption, however.^[4] The decrease in rifampin 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 CSF. 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 proteins.^[19]

Interactions[edit]

Rifampicin is an inducer of many enzymes of the cytochrome P450 superfamily, including CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4, CYP3A5, and CYP3A7.^[20] Thus it will speed up the metabolism of any drug metabolized by any of these enzymes in the body. Other possible interactions which may not be listed include antiretroviral agents, everolimus, atorvastatin, rosiglitazone/pioglitazone, celecoxib, clarithromycin, caspofungin, and lorazepam.^[21]

Rifampicin is antagonistic to the effect of gentamycin and amikacin.

Preparations[edit]

Rifampicin is available in:

Bulgaria as Tubocin (by Actavis/Balkanpharma)
Romania as Sinerdol (Sicomed)
UK as Rifadin (Aventis), Rimactan (Sandoz), Rifater (a combination with isoniazid and pyrazinamide) (Aventis), Rifinah (a combination with isoniazid) (Aventis), and Rimactazid (a combination with isoniazid) (Sandoz)
U.S. as Rifadin (Aventis), Rifater (combination with isoniazid and pyrazinamide) (Aventis), Rimactane (Novartis)
France as Rifadine (Aventis)
India R-Cinex 600 (Lupin Limited)/Micox (a combination of rifampicin and isoniazid)
Australia as Rimycin (Alphapharm)
Egypt as Rimactan (Sandoz)
Germany as Eremfat (Riemser)

References[edit]

^ Masters, Susan B.; Trevor, Anthony J.; Katzung, Bertram G. (2005). Katzung & Trevor's pharmacology. New York: Lange Medical Books/McGraw Hill, Medical Pub. Division. ISBN 0-07-142290-0.
^ Sensi P, Margalith P, Timbal MT (1959). "Rifomycin, a new antibiotic—preliminary report". Farmaco Ed Sci 14: 146–147.
^ "When I Use a Word . . .I Mean It". British Medical Journal 1999;319(7215):972 (9 October). Retrieved 2009-07-10.
^ ^a ^b "Kinetics of Rifampin taken with food and with antacids" (PDF). Retrieved 2011-11-07.
^ ^a ^b Long, James W. (1991). Essential Guide to Prescription Drugs 1992. New York: HarperCollins Publishers. pp. 925–929. ISBN 0-06-273090-8.
^ Erlich, Henry, W Ford Doolittle, Volker Neuhoff, and et al. . Molecular Biology of Rifomycin. New York, NY: MSS Information Corporation, 1973. pp. 44-45, 66-75, 124-130.
^ Hofmann, AF (2002). "Rifampicin and treatment of cholestatic pruritus". Gut 51 (5): 756–757. doi:10.1136/gut.51.5.756. PMC 1773428. PMID 12377823. More than one of |work= and |journal= specified (help)
^ 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. doi:10.1111/j.1469-0691.2007.01691.x. PMID 17331125.
^ 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. doi:10.1086/508667. PMID 17029130.
^ 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. doi:10.1586/eri.09.44. PMC 2739015. PMID 19681699.
^ 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. doi:10.1016/j.virol.2006.09.031. PMC 1817899. PMID 17055024.
^ 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". J. Virol. 68 (2): 1103–14. PMC 236549. PMID 8289340.
^ Calvori, C.; Frontali, L.; Leoni, L.; Tecce, G. (1965). "Effect of rifamycin on protein synthesis". Nature 207 (995): 417–8. doi:10.1038/207417a0. PMID 4957347.
^ Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., Darst, S.A. (2001). "Structural mechanism for rifampicin inhibition of bacterial RNA polymerase". Cell 104 (6): 901–12. doi:10.1016/S0092-8674(01)00286-0. PMID 11290327.
^ ^a ^b Feklistov, A., Mekler, V., Jiang, Q., Westblade, L.F., Irschik, H., Jansen, R., Mustaev, A., Darst, S.A., Ebright, R.H. (2008). "Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center". Proc Natl Acad Sci USA 105 (39): 14820–5. doi:10.1073/pnas.0802822105. PMC 2567451. PMID 18787125.
^ Collins, R Douglas. Atlas of Drug Reactions. New York, NY: ChurchillLivingstone, 1985. pp. 123.
^ Stockley, Ivan H. "Anticoagulant Drug Interactions." Drug Interactions. 3rd ed. Boston: Blackwell Scientific Publications, 1994. pp. 274-275.
^ G Curci, A Ninni, A.D'Aleccio (1969) Atti Tavola Rotonda Rifampicina, Taormina, page 19. Edizioni Rassegna Medica, Lepetit, Milano
^ 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.
^ "Division of Clinical Pharmacology | Indiana University Department of Medicine". Medicine.iupui.edu. 2011-09-27. Retrieved 2011-11-07.
^ Riss, J.; Cloyd, J.; Gates, J.; Collins, S. (Aug 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics". Acta Neurol Scand 118 (2): 69–86. doi:10.1111/j.1600-0404.2008.01004.x. PMID 18384456.

streptomycetes for Mediterranean...RNA polymerase

External links[edit]

Rifampicin bound to proteins in the PDB
PubPK - Rifampicin pharmacokinetics
Prescribing Information for RIFADIN by Sanofi-Aventis
U.S. National Library of Medicine: Drug Information Portal - Rifampicin
PDR.net Concise Monograph - Rifadin

UpToDate Contents

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English Journal

Clinical and Bacteriological Efficacy of Rifampin-Streptomycin Combination for Two Weeks followed by Rifampin and Clarithromycin for Six Weeks for Treatment of Mycobacterium ulcerans Disease.

Phillips RO1, Sarfo FS, Abass MK, Abotsi J, Wilson T, Forson M, Amoako YA, Thompson W, Asiedu K, Wansbrough-Jones M.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2014 Apr;58(4):2488.
PMID 24643845

Combination Prophylactic Therapy with Rifampin Increases Efficacy against an Experimental Staphylococcus epidermidis Subcutaneous Implant-Related Infection.

Stavrakis AI1, Niska JA, Shahbazian JH, Loftin AH, Ramos RI, Billi F, Francis KP, Otto M, Bernthal NM, Uslan DZ, Miller LS.Author information 1Orthopaedic Hospital Research Center (OHRC), UCLA/Orthopaedic Hospital-Department of Orthopaedic Surgery, David Geffen School of Medicine at University of California, Los Angeles (UCLA), Los Angeles, California, USA.AbstractThe incidence of infections related to cardiac devices (such as permanent pacemakers) has been increasing out of proportion to implantation rates. As management of device infections typically requires explantation of the device, optimal prophylactic strategies are needed. Cefazolin and vancomycin are widely used as single agents for surgical prophylaxis against cardiac device-related infections. However, combination antibiotic prophylaxis may further reduce infectious complications. To model a localized subcutaneous implant-related infection, a bioluminescent strain of Staphylococcus epidermidis was inoculated onto a medical-procedure-grade titanium disc, which was placed into a subcutaneous pocket in the backs of mice. In vivo bioluminescence imaging, quantification of ex vivo CFU from the capsules and implants, variable-pressure scanning electron microscopy (VP-SEM), and neutrophil enhanced green fluorescent protein (EGFP) fluorescence in LysEGFP mice were employed to monitor the infection. This model was used to evaluate the efficacies of low- and high-dose cefazolin (50 and 200 mg/kg of body weight) and vancomycin (10 and 110 mg/kg) intravenous prophylaxis with or without rifampin (25 mg/kg). High-dose cefazolin and high-dose vancomycin treatment resulted in almost complete bacterial clearance, whereas both low-dose cefazolin and low-dose vancomycin reduced the in vivo and ex vivo bacterial burden only moderately. The addition of rifampin to low-dose cefazolin and vancomycin was highly effective in further reducing the CFU harvested from the implants. However, vancomycin-rifampin was more effective than cefazolin-rifampin in further reducing the CFU harvested from the surrounding tissue capsules. Future studies in humans will be required to determine whether the addition of rifampin has improved efficacy in preventing device-related infections in clinical practice.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2014 Apr;58(4):2377-2386. Epub 2014 Feb 10.
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PMID 24514089

Novel Regimens Identified in Mice for Treatment of Latent Tuberculosis Infection in Contacts of Patients with Multidrug-Resistant Tuberculosis.

Lanoix JP1, Betoudji F, Nuermberger E.Author information 1Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.AbstractPreventing the development of tuberculosis (TB) in contacts of patients with multidrug-resistant TB (MDR-TB) by the treatment of latent TB infection (LTBI) is highly desirable. However, few safe, well tolerated, and effective drugs are available to treat MDR-LTBI and the published guidance is limited. Fortunately, six new chemical entities from four classes developed to treat TB have entered clinical trials in the past decade. We tested three of these drugs alone and in combination in an experimental paucibacillary LTBI chemotherapy model using BALB/c and C3HeB/FeJ mice immunized with a recombinant strain of Mycobacterium bovis bacillus Calmette-Guérin (rBCG30) and then challenged with a low-dose aerosol of M. tuberculosis H37Rv. The regimens tested contained bedaquiline (TMC), PA-824 (Pa), sutezolid (PNU), and/or one of two fluoroquinolones. Control mice received rifampin (RIF) or isoniazid (INH). In BALB/c mice, TMC-containing regimens and the Pa-PNU combination were the most active test regimens and were at least as effective as RIF. Pa, PNU, and levofloxacin had activity comparable to that of INH. Virtually identical results were observed in C3HeB/FeJ mice. This study confirms the potent activity of TMC observed previously in BALB/c mice and highlights Pa alone or in combination with either PNU or a fluoroquinolone as a regimen worthy of evaluation in future clinical trials of MDR-LTBI. Given their closer pathological representation of human TB lesions, C3HeB/FeJ mice may become a preferred model for the experimental chemotherapy of LTBI. Future studies should evaluate additional clinically relevant LTBI regimens in this strain including relapse as an endpoint.
Antimicrobial agents and chemotherapy.Antimicrob Agents Chemother.2014 Apr;58(4):2316-2321. Epub 2014 Feb 3.
Preventing the development of tuberculosis (TB) in contacts of patients with multidrug-resistant TB (MDR-TB) by the treatment of latent TB infection (LTBI) is highly desirable. However, few safe, well tolerated, and effective drugs are available to treat MDR-LTBI and the published guidance is limite
PMID 24492372

Japanese Journal

A Case of Pneumothorax Complicated by Multiple Large Pulmonary Nodules Due to Mycobacterium Kansasii Infection

Showa Univ J Med Sci 27(4), 297-304, 2015-12
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術前管理に苦慮した肺結核併存原発性アルドステロン症の1例

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★リンクテーブル★

リンク元

「リファンピシン」

Rifampicin
Systematic (IUPAC) name
	(7S,9E,11S,12R,13S,14R,15R,16R,17S,18S,19E,21Z)-2,15,17,27,29-pentahydroxy-11-methoxy-3,7,12,14,16,18,22-heptamethyl-26-{(E)-[(4-methylpiperazin-1-yl)imino]methyl}-6,23-dioxo-8,30-dioxa-24-azatetracyclo[23.3.1.14,7.05,28]triaconta-1(28),2,4,9,19,21,25(29),26-octaen-13-yl acetate
Clinical data
Trade names	Rifadin
AHFS/Drugs.com	International Drug Names
MedlinePlus	a682403
Pregnancy cat.	C (AU)
Legal status	Prescription Only (S4) (AU) POM (UK)
Routes	Oral, IV
Pharmacokinetic data
Bioavailability	90 to 95%
Metabolism	Hepatic and intestinal wall
Half-life	1.5 to 5 hours
Excretion	15 to 30% renal; 60% faecal
Identifiers
CAS number	13292-46-1
ATC code	J04AB02 QJ54AB02
PubChem	CID 5360416
IUPHAR ligand	2765
DrugBank	DB01045
ChemSpider	10468813
UNII	VJT6J7R4TR
KEGG	D00211
ChEBI	CHEBI:28077
ChEMBL	CHEMBL180
NIAID ChemDB	007228
Synonyms	5,6,9,17,19,21-Hexahydroxy-23-methoxy-2,4,12,16,18,20,22-heptamethyl-8-[N-(4-methyl-1-piperazinyl)formimidoyl]-2,7-(epoxypentadeca[1,11,13]trienimino)-naphtho[2,1-b]furan-1,11(2H)-dione 21-acetate
Chemical data
Formula	C43H58N4O12
Mol. mass	822.94 g/mol
	SMILES CN1CCN(CC1)/N=C/c2c(O)c3c5C(=O)[C@@]4(C)O/C=C/[C@H](OC)[C@@H](C)[C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(\C)C(=O)Nc2c(O)c3c(O)c(C)c5O4;
	InChI InChI=1S/C43H58N4O12/c1-21-12-11-13-22(2)42(55)45-33-28(20-44-47-17-15-46(9)16-18-47)37(52)30-31(38(33)53)36(51)26(6)40-32(30)41(54)43(8,59-40)57-19-14-29(56-10)23(3)39(58-27(7)48)25(5)35(50)24(4)34(21)49/h11-14,19-21,23-25,29,34-35,39,49-53H,15-18H2,1-10H3,(H,45,55)/b12-11+,19-14+,22-13-,44-20+/t21-,23+,24+,25+,29-,34-,35+,39+,43-/m0/s1 ; Key:JQXXHWHPUNPDRT-WLSIYKJHSA-N ;
Physical data
Melt. point	183–188 °C (361–370 °F)
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　　[★]

英: rifampicin, RFP, RIF
商: Rifampin、リファジン、リマクタン、アプテシン
関: 抗結核薬、結核、抗菌薬

分類

抗結核薬

特徴

濃度依存性　　←　アミノグリコシドlike
血漿濃度より組織内の方が高濃度に分布し、マクロファージに潜伏する結核菌に有効に作用。

薬理作用

抗菌作用：結核菌に対する抗菌力はイソニアジドに匹敵。

作用機序

結核菌のDNA依存RNAポリメラーゼに作用し、RNA合成初期段階を阻害(参考2)

注意

副作用

他の抗結核菌薬と比べて特異的なものはない。

白血球減少、血小板減少、発疹、肝障害

参考1

胃腸症状(悪心、嘔吐、下痢)、中枢神経系(頭痛、発熱)、皮膚(皮疹、掻痒、発赤)、血液系の異常(血小板減少症、急性溶血性貧血)
イソニアジドなどの肝毒性を有する薬剤との同時投与により肝炎を来しやすい。
掻痒症も来すことがある。観血的に高用量を用いた患者にインフルエンザ様症状出現の報告がある。
体液(汗、唾液、涙)がオレンジ～橙赤色になる。

参考

1. [charged] Rifampin and other rifamycins - uptodate
2. リファジンカプセル１５０ｍｇ - 添付文書

http://www.info.pmda.go.jp/go/pack/6164001M1216_1_03/6164001M1216_1_03

[isbn0-07-142290-0-1] Masters, Susan B.; Trevor, Anthony J.; Katzung, Bertram G. (2005). Katzung & Trevor's pharmacology. New York: Lange Medical Books/McGraw Hill, Medical Pub. Division. ISBN 0-07-142290-0.

[2] Sensi P, Margalith P, Timbal MT (1959). "Rifomycin, a new antibiotic—preliminary report". Farmaco Ed Sci 14: 146–147.

[BMJ-3] "When I Use a Word . . .I Mean It". British Medical Journal 1999;319(7215):972 (9 October). Retrieved 2009-07-10.

[chestjournal.chestpubs.org-4] "Kinetics of Rifampin taken with food and with antacids" (PDF). Retrieved 2011-11-07.

[isbn0-06-273090-8-5] Long, James W. (1991). Essential Guide to Prescription Drugs 1992. New York: HarperCollins Publishers. pp. 925–929. ISBN 0-06-273090-8.

[Erlich-6] Erlich, Henry, W Ford Doolittle, Volker Neuhoff, and et al. . Molecular Biology of Rifomycin. New York, NY: MSS Information Corporation, 1973. pp. 44-45, 66-75, 124-130.

[pmid12377823-7] Hofmann, AF (2002). "Rifampicin and treatment of cholestatic pruritus". Gut 51 (5): 756–757. doi:10.1136/gut.51.5.756. PMC 1773428. PMID 12377823. More than one of |work= and |journal= specified (help)

[8] 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. doi:10.1111/j.1469-0691.2007.01691.x. PMID 17331125.

[pmid_17029130-9] 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. doi:10.1086/508667. PMID 17029130.

[10] 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. doi:10.1586/eri.09.44. PMC 2739015. PMID 19681699.

[pmid17055024-11] 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. doi:10.1016/j.virol.2006.09.031. PMC 1817899. PMID 17055024.

[pmid8289340-12] 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". J. Virol. 68 (2): 1103–14. PMC 236549. PMID 8289340.

[13] Calvori, C.; Frontali, L.; Leoni, L.; Tecce, G. (1965). "Effect of rifamycin on protein synthesis". Nature 207 (995): 417–8. doi:10.1038/207417a0. PMID 4957347.

[Campbell-14] Campbell, E.A., Korzheva, N., Mustaev, A., Murakami, K., Nair, S., Goldfarb, A., Darst, S.A. (2001). "Structural mechanism for rifampicin inhibition of bacterial RNA polymerase". Cell 104 (6): 901–12. doi:10.1016/S0092-8674(01)00286-0. PMID 11290327.

[Feklistov-15] Feklistov, A., Mekler, V., Jiang, Q., Westblade, L.F., Irschik, H., Jansen, R., Mustaev, A., Darst, S.A., Ebright, R.H. (2008). "Rifamycins do not function by allosteric modulation of binding of Mg2+ to the RNA polymerase active center". Proc Natl Acad Sci USA 105 (39): 14820–5. doi:10.1073/pnas.0802822105. PMC 2567451. PMID 18787125.

[Collins-16] Collins, R Douglas. Atlas of Drug Reactions. New York, NY: ChurchillLivingstone, 1985. pp. 123.

[17] Stockley, Ivan H. "Anticoagulant Drug Interactions." Drug Interactions. 3rd ed. Boston: Blackwell Scientific Publications, 1994. pp. 274-275.

[18] G Curci, A Ninni, A.D'Aleccio (1969) Atti Tavola Rotonda Rifampicina, Taormina, page 19. Edizioni Rassegna Medica, Lepetit, Milano

[Hardman-19] 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.

[drug-interactions.com-20] "Division of Clinical Pharmacology | Indiana University Department of Medicine". Medicine.iupui.edu. 2011-09-27. Retrieved 2011-11-07.

[21] Riss, J.; Cloyd, J.; Gates, J.; Collins, S. (Aug 2008). "Benzodiazepines in epilepsy: pharmacology and pharmacokinetics". Acta Neurol Scand 118 (2): 69–86. doi:10.1111/j.1600-0404.2008.01004.x. PMID 18384456.

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Rifampin