Rifabutin

Rifabutin
Names
Trade namesMycobutin[1]
IUPAC name
  • (9S,12E,14S,15R,16S,17R,18R,19R,20S,
    21S,22E,24Z)-6,16,18,20-tetrahydroxy-1'-
    isobutyl-14-methoxy-7,9,15,17,19,21,25-
    hepta-methyl-spiro[9,4-(epoxypentadeca
    [1,11,13]trienimino)-2H-furo-[2',3':7,8]-naphth
    [1,2-d]imidazol-2,4'-piperidin]-5,10,26-(3H,9H)-
    trione-16-acetate
Clinical data
WHO AWaReUnlinkedWikibase error: ⧼unlinkedwikibase-error-statements-entity-not-set⧽
Pregnancy
category
  • AU: C
  • US: B (No risk in non-human studies)
    Routes of
    use    		by mouth (capsules)
    Defined daily dose0.15 grams[2]
    External links
    AHFS/Drugs.comMonograph
    MedlinePlusa693009
    Legal
    Legal status
    Pharmacokinetics
    Bioavailability85%
    Protein binding85%
    Metabolismliver
    Elimination half-life28 to 62 hours (mean)
    Excretionkidney and fecal
    Chemical and physical data
    FormulaC46H62N4O11
    Molar mass847.019 g·mol−1
    3D model (JSmol)
    SMILES
    • C[C@H]1/C=C\C=C(/C(=O)NC2=C3C(=NC4(N3)CCN(CC4)CC(C)C)C5=C6C(=C(C(=C5C2=O)O)C)O[C@@](C6=O)(O/C=C\[C@@H]([C@H]([C@H]([C@@H]([C@@H]([C@@H]([C@H]1O)C)O)C)OC(=O)C)C)OC)C)\C
    InChI
    • InChI=1S/C46H62N4O11/c1-22(2)21-50-18-16-46(17-19-50)48-34-31-32-39(54)28(8)42-33(31)43(56)45(10,61-42)59-20-15-30(58-11)25(5)41(60-29(9)51)27(7)38(53)26(6)37(52)23(3)13-12-14-24(4)44(57)47-36(40(32)55)35(34)49-46/h12-15,20,22-23,25-27,30,37-38,41,49,52-54H,16-19,21H2,1-11H3,(H,47,57)/b13-12+,20-15+,24-14-/t23-,25+,26+,27+,30-,37-,38+,41+,45-/m0/s1 checkY
    • Key:ATEBXHFBFRCZMA-VXTBVIBXSA-N checkY

    Rifabutin (Rfb) is an antibiotic used to treat tuberculosis and prevent and treat Mycobacterium avium complex.[1] It is typically only used in those who cannot tolerate rifampin such as people with HIV/AIDS on antiretrovirals.[1] For active tuberculosis it is used with other antimycobacterial medications.[1] For latent tuberculosis it may be used by itself when the exposure was with drug-resistant TB.[1]

    Common side effects include abdominal pain, nausea, rash, headache, and low blood neutrophil levels.[1] Other side effects include muscles pains and uveitis.[1] While no harms have been found during pregnancy it has not been well studied in this population.[1] Rifabutin is in the rifamycin family of medications.[1] It by blocking RNA production in bacteria.[3]

    Rifabutin was approved for medical use in the United States in 1992.[1] It is on the World Health Organization's List of Essential Medicines.[4] The wholesale cost in the developing world is about US$30 a month.[5] In the United States a month of treatment is more than $200.[6]

    Medical uses

    Rifabutin is now recommended as first-line treatment for tuberculosis,[7] but rifampicin was used more widely because of its cheaper cost. However, due to the expiration of patents, prices are now similar.

    Rifabutin is used in the treatment of Mycobacterium avium complex disease, a bacterial infection most commonly encountered in people with late-stage AIDS. Its main usefulness lies in the fact that it has fewer drug interactions than rifampicin; therefore people with HIV/AIDS on HAART are usually given rifabutin for treatment of TB.

    Rifabutin is well tolerated in people with HIV-related tuberculosis (TB), but new findings suggest that with low CD4 cell counts have a high risk of treatment failure or relapse due to acquired rifamycin resistance. Since patients co-infected with TB and HIV/AIDS are likely to get TB treated first, when the CD4 is suppressed at the time TB treatment begins, doctors and patients should be aware of a possible rifamycin resistance.

    Rifabutin is also being investigated in trials for treating Crohn's disease as part of the anti-MAP therapy. In a Phase III study administering sub-therapeutic doses of rifabutin in combination therapy to patients not identified with MAP infections, it was associated with significant short term benefits.[8][9]

    It has also found to be useful in the treatment of Chlamydophila pneumoniae (Cpn) infection.

    Dosage

    The defined daily dose is 0.15 grams (by mouth)[2]

    History

    Scientists at the Italian drug company Achifar discovered rifabutin in 1975. (Eventually Archifar became part of Farmitalia Carlo Erba, a unit of the conglomerate Montedison which was subsequently bought by Pharmacia) This company's Adria Laboratories subsidiary filed for Food and Drug Administration (FDA) approval of rifabutin under the brand name Mycobutin in the early 1990s and the drug gained FDA approval in December 1992.

    Rifabutin is primarily bactericidal antibiotic drug used to treat tuberculosis. Its effect on bacteria is based on the DNA-dependent RNA polymerase blocking drug rifamycin S, a semi-synthetic derivative. It is effective, for example, in highly resistant mycobacteria, Gram-positive bacteria (and some are effective against Gram-negative bacteria), but also against Mycobacterium tuberculosis, M. leprae, and M. avium intracellulare.

    References

    1. 1 2 3 4 5 6 7 8 9 10 "Rifabutin". The American Society of Health-System Pharmacists. Archived from the original on 20 December 2016. Retrieved 8 December 2016.
    2. 1 2 "WHOCC - ATC/DDD Index". www.whocc.no. Archived from the original on 24 August 2019. Retrieved 21 September 2020.
    3. ↑ Rockwood, Neesha; Cerrone, Maddalena; Barber, Melissa; Hill, Andrew M; Pozniak, Anton L (18 July 2019). "Global access of rifabutin for the treatment of tuberculosis – why should we prioritize this?". Journal of the International AIDS Society. 22 (7): e25333. doi:10.1002/jia2.25333. PMC 6637439. PMID 31318176. Rifabutin is a rifamycin, which like rifampicin, works via inhibition of DNA‐dependent RNA synthesis in prokaryotes.
    4. ↑ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
    5. ↑ "Rifabutin". International Drug Price Indicator Guide. Archived from the original on 22 January 2018. Retrieved 8 December 2016.
    6. ↑ Hamilton, Richart (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 50. ISBN 9781284057560.
    7. ↑ Guidelines for the programmatic management of drug-resistant tuberculosis: emergency update 2008 (WHO/HTM/TB/2008.402). Geneva, Switzerland: World Health Organization. 2008. p. ix. ISBN 978-92-4-154758-1. Archived from the original on 2008-10-18.
    8. ↑ Selby, Warwick; Pavli, Paul; Crotty, Brendan; Florin, Tim; Radford-Smith, Graham; Gibson, Peter; Mitchell, Brent; Connell, William; Read, Robert; Merrett, Michael; Ee, Hooi; Hetzel, David; Antibiotics in Crohn's Disease Study Group (June 2007). "Two-Year Combination Antibiotic Therapy With Clarithromycin, Rifabutin, and Clofazimine for Crohn's Disease". Gastroenterology. 132 (7): 2313–2319. doi:10.1053/j.gastro.2007.03.031. PMID 17570206.
    9. ↑ Kuenstner, J. Todd (November 2007). "The Australian Antibiotic Trial in Crohn's Disease: Alternative Conclusions From the Same Study". Gastroenterology. 133 (5): 1742–1743. doi:10.1053/j.gastro.2007.09.012. PMID 17983824.
    External sites:
    Identifiers:


    This article is issued from Offline. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.