Rifabutin (Rfb) is a medicine, a broad-spectrum antibiotic , mainly used to treat tuberculosis [1] [5] and to prevent infection of HIV-infected patients with Mycobacterium avium complex bacteria. [6]
| Rifabutin | |
|---|---|
| Rifabutin [1] | |
 | |
| Chemical compound | |
| IUPAC | 1 ', 4-Didehydro-1-deoxy-1,4-dihydro-5' - (2-methylpropyl) -1-oxorifamycin XIV |
| Gross formula | C 46 H 62 N 4 O 11 |
| Molar mass | 847.02 |
| Cas | |
| PubChem | |
| Drugbank | |
| Classification | |
| Farmakol. Group | Ansamycins [2] |
| ATX | -> |
| Pharmacokinetics | |
| Plasma Protein Binding | 85% |
| Metabolism | liver |
| Excretion | It is excreted in the urine in the form of metabolites and unchanged (≈10% [3] ), the elimination half-life is 35-40 hours |
| Dosage Forms | |
| capsules | |
| Other names | |
| Verbutin, Mikobutin, Farbutin [4] | |
Content
History
Scientists from the Italian pharmaceutical company Achifar discovered rifabutin in 1975 . Subsequently, Archifar became part of Farmitalia Carlo Erba , a division of Montedison Corporation. In the early 90s, the Adria laboratory applied for certification with the Food and Drug Administration (FDA ). In December 1992, rifabutin was registered under the Mikobutin trademark.
Properties
Spiro piperidyl derivative of rifamycin S, highly lipophilic compound. Red violet powder. Soluble in chloroform and methyl alcohol , sparingly soluble in ethyl alcohol , practically insoluble in water. [2]
Pharmacology
It has a wide spectrum of action. The mechanism of action is probably associated with inhibition of amino acid synthesis due to inhibition of DNA-dependent RNA polymerase. Rifabutin is active against Mycobacterium tuberculosis (both sensitive and rifampicin-resistant strains), Mycobacterium leprae (both sensitive and rifampicin-resistant strains), against the Mycobacterium avium complex. Rifabutin is also active against gram-positive bacteria: Staphylococcus spp. (including multiresistant), some strains of Clostridium spp .; gram-negative bacteria: Neisseria meningitidis, Neisseria gonorrhoeae, Haemophilus influenzae, Legionella spp., Chlamydia trachomatis; intracellular parasites; some viruses (including HIV-1). The resistance of pathogen strains to rifabutin is developing rapidly. [7]
Absorbed from the digestive tract faster than rifampicin due to greater fat solubility. [8] Bioavailability is 20%. Cmax in plasma is reached after 2-4 hours. Binding to plasma proteins is 85%. Penetrates through the BBB. T1 / 2 - 45 hours. 30% of rifabutin is excreted in the feces, 5% - unchanged with bile, 5% - unchanged with urine, 53% - with urine in the form of metabolites.
Application
Rifabutin is positioned as an alternative to rifampicin, which is a first-line anti-TB drug .
Rifabutin can be used instead of rifampicin as part of combination therapy in the treatment of tuberculosis caused by multiresistant strains of M. tuberculosis , and the presence of incomplete cross-resistance of mycobacteria to both drugs must be taken into account. [3] [9] [10] [11] Its effectiveness against resistant strains is due to its ability to penetrate better into cells [3] [12] and its ability to influence the biosynthesis of DNA of mycobacteria in concentrations from eight [13] to forty [14 ] times lower than rifampicin concentrations. [13] Moreover, prolonged use of rifabutin rarely leads to the emergence of resistance to this drug. [14] [15]
However, according to some reports, there are no significant differences in the use of rifampicin and rifabutin in the treatment of tuberculosis and the prevention of relapse. [sixteen]
Rifabutin also has the potential to be used to treat tuberculosis in HIV-infected patients due to the lack of interaction with antiretroviral agents. At the same time, there is a need for clinical trials of adequate quality to verify this aspect of the use of the drug. [sixteen]
Side
Like rifampicin , it stains urine orange or red. When taken with clarithromycin , the risk of developing uveitis increases . Significantly reduces the effectiveness of oral contraceptives [17] , other contraceptives should be used during rifabutin. [18]
Notes
- ↑ 1 2 Rifabutin. Radar drug reference: instructions for use and description of the substance Rifabutin
- ↑ 1 2 Rifabutin . Register of medicines . ReLeS.ru (April 9, 2007). Date of treatment August 18, 2010. Archived February 4, 2012.
- ↑ 1 2 3 http://www.doc.state.ok.us/treatment/medical/msrm/140301.04%20L.pdf
- ↑ http://www.boinc.org/rifabutin/ Description of the drug on boinc.org
- ↑ Scientific Network >> Long-acting anti-tuberculosis antibiotic rifabutin. Antimicrobial spectrum, features of pharmacodynamics and pharmacokinetics
- ↑ Rifabutin - Compound Summary . PubChem . The National Library of Medicine (November 29, 2005). Date of treatment August 18, 2010. Archived February 4, 2012.
- ↑ Search the database of drugs, search options: INN - Rifabutin , the flags “Search in the register of registered drugs” , “Search TKFS” , “Show drug forms” unspecified (inaccessible link) . Circulation of drugs . Federal State Institution “Scientific Center for Expertise of Medical Application Tools” of the Russian Healthcare Supervision Authority of the Russian Federation (August 23, 2010). - A typical clinical and pharmacological article is a by-law and is not protected by copyright in accordance with part four of the Civil Code of the Russian Federation No. 230-FZ of December 18, 2006. Date of treatment April 28, 2011. Archived August 22, 2011.
- ↑ Blaschke TF, Skinner MH The clinical pharmacokinetics of rifabutin (English) // Clin. Infect. Dis. : journal. - 1996 .-- April ( vol. 22 Suppl 1 ). - P. S15-21; discussion S21-2 . - PMID 8785251 .
- ↑ Petr Prokofievich Denisenko. Modern medicines: Clinical and pharmacological directory of a practical doctor . - 2. - Olma Media Group, 2003 .-- S. 388. - 864 p. - ISBN 5765427383 , 9785765427385.
- ↑ http://ros-med.info Description of the drug
- ↑ http://www.med.by/methods/pdf/28-9902.pdf
- ↑ http://www.ifp.kiev.ua/doc/journals/upj/08/pdf08-3/49.pdf
- ↑ 1 2 ANTITUBERCULOSIVE PRODUCTS | New Drug Reference
- ↑ 1 2 Tuberculosis: new possibilities in treatment / Pulmonology / Medical articles
- ↑ Treatment of drug-resistant tuberculosis
- ↑ 1 2 Davies GR, Cerri S., Richeldi L. Rifabutin for treating pulmonary tuberculosis (English) . Cochrane Database of Systematic Reviews 2007, Issue 4. Art. No .: CD005159. DOI: 10.1002 / 14651858.CD005159.pub2 . The Cochrane Collaboration (July 5, 2007). Date of treatment August 18, 2010. Archived February 4, 2012.
- ↑ Finch CK, Chrisman CR, Baciewicz AM, Self TH Rifampin and rifabutin drug interactions: an update (Eng.) // Arch. Intern. Med. : journal. - 2002 .-- May ( vol. 162 , no. 9 ). - P. 985–992 . - PMID 11996607 .
- ↑ Mycobutin. Description of the drug
See also
- Arbutin
- Rifapentin
Literature
- Tsybanev A.A., Sokolova G. B. Long-acting antituberculous antibiotic - rifabutin. Antimicrobial spectrum, features of pharmacodynamics and pharmacokinetics // Antibiotics and chemotherapy. - 1999. - No. 8 . - S. 30-36 .