Chemical formula: C₄₆H₆₂N₄O₁₁ Molecular mass: 847.005 g/mol PubChem compound: 6323490
In vitro activity of rifabutin against laboratory strains and clinical isolates of M. tuberculosis has been shown to be very high. In vitro studies carried out so far have shown that from one-third to half of M.tuberculosis strains resistant to rifampicin are susceptible to rifabutin, indicating that cross-resistance between the two antibiotics is incomplete.
The in vivo activity of rifabutin on experimental infections caused by M. tuberculosis was about 10 times greater than that of rifampicin in agreement with the in vitro findings.
Rifabutin was seen to be active against non-tuberculous (atypical) mycobacteria including M. avium-intracellulare (MAC), in vitro as well as in experimental infections caused by these pathogens in mice with induced immuno-deficiency.
In man, rifabutin is rapidly absorbed and maximum plasma concentrations are reached around 2-4 hours after oral administration. The pharmacokinetics of rifabutin is linear after single administration of 300, 450, and 600 mg to healthy volunteers. With these doses, Cmax is in the range of 0.4-0.7 µg/ml. Plasma concentrations are maintained above the MIC values for M. tuberculosis up to about 30 hours from administration.
Rifabutin is widely distributed in various animal organs with the exception of the brain. In particular, in human lung tissue the concentrations measured up to 24 hours after dosing were about 5-10 times higher than the plasma levels.
The intracellular penetration of rifabutin is very high as demonstrated by intracellular/extracellular concentration ratios which ranged from 9 in neutrophils to 15 in monocytes, both obtained from human sources.
The high intracellular concentration is likely to play a crucial role in sustaining the efficacy of rifabutin against intracellular pathogens such as mycobacteria.
Rifabutin and its metabolites are eliminated mainly by the urinary route. The t½ of rifabutin in man is approximately 35-40 hours.
Preclinical safety studies of rifabutin indicate a good safety margin in rodents and in monkeys.
In repeated dose studies, target organs were identified at doses producing blood levels higher than those achieved with recommended doses for human therapy. The main target organs are liver and, to a lesser degree, erythrocytes.
Rifabutin did not show any teratogenic, mutagenic or carcinogenic potential.
© All content on this website, including data entry, data processing, decision support tools, "RxReasoner" logo and graphics, is the intellectual property of RxReasoner and is protected by copyright laws. Unauthorized reproduction or distribution of any part of this content without explicit written permission from RxReasoner is strictly prohibited. Any third-party content used on this site is acknowledged and utilized under fair use principles.
