Rifabutin

Rifabutin

Systematic (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
Trade names	Mycobutin
AHFS/Drugs.com	monograph
MedlinePlus	a693009
Pregnancy cat.	C (Australia), B (United States)
Legal status	POM (UK), ℞-only (U.S.)
Routes	Oral
Pharmacokinetic data
Bioavailability	85%
Protein binding	85%
Metabolism	Hepatic
Half-life	28 to 62 hours (mean)
Excretion	Renal and fecal
Identifiers
CAS number	72559-06-9 Y
ATC code	J04AB04
PubChem	CID 6323490
DrugBank	APRD00094
ChemSpider	10482168 Y
UNII	1W306TDA6S N
KEGG	D00424 N
ChEBI	CHEBI:45367 N
ChEMBL	CHEMBL444633 Y
Chemical data
Formula	C46H62N4O11
Mol. mass	847.005 g/mol
SMILES	eMolecules & PubChem
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 Y Key:ATEBXHFBFRCZMA-VXTBVIBXSA-N Y
N(what is this?)  (verify)

Rifabutin (Rfb) is a bactericidal antibiotic drug primarily used in the treatment of tuberculosis. The drug is a semi-synthetic derivative of rifamycin S. Its effect is based on blocking the DNA-dependent RNA-polymerase of the bacteria. It is effective against Gram-positive and some Gram-negative bacteria, but also against the highly resistant Mycobacteria, e.g. Mycobacterium tuberculosis, M. leprae and M. avium intracellulare.

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

Indications

Rifabutin is now recommended as first-line treatment for tuberculosis.^[1] Rifampicin is more widely used because of its cheaper cost.

Rifabutin is used in the treatment of mycobacterium avium complex disease, a bacterial infection most commonly encountered in late-stage AIDS patients.

Rifabutin is well tolerated in patients with HIV-related tuberculosis (TB), but patients with low CD4 cell counts have a high risk of treatment failure or relapse due to acquired rifamycin resistance, a new study found.

Since patients co-infected with TB and HIV / AIDS are likely to get TB treated first, doctors and patients should be aware of a possible rifamycin resistance issue, if the CD4 is so suppressed at the time TB treatment is to begin.

Rifabutin is also used in trials for treating Crohn's Disease as part of the anti-MAP therapy. In a Phase 3 study it could not prove a significant role of MAP in Crohn's disease.^[2]

Its main usefulness lies in the fact that it has lesser drug interactions than rifampicin therefore HIV infected patients on HAART are given rifabutin for treatment of TB

It has also found to be useful in the treatment of (Chlamydia) Chlamydophila pneumoniae (Cpn) Infection. See external link.

Supply

.

References

1. ^ 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. http://www.who.int/tb/publications/2008/programmatic_guidelines_for_mdrtb/en/index.html. 
2. ^ . doi:10.1053/j.gastro.2007.03.031. PMID 17570206. 

External links

• U.S. Patent 3,150,046 to Achifar.

• Chlamydia Pneumoniae cpnhelp.org