| Indication |
For the prevention of disseminated Mycobacterium avium complex (MAC) disease in patients with advanced HIV infection. |
| Pharmacodynamics |
Rifabutin is an antibiotic that inhibits DNA-dependent RNA
polymerase activity in susceptible cells. Specifically, it interacts
with bacterial RNA polymerase but does not inhibit the mammalian enzyme.
It is bactericidal and has a very broad spectrum of activity against
most gram-positive and gram-negative organisms (including Pseudomonas aeruginosa) and specifically Mycobacterium tuberculosis.
Because of rapid emergence of resistant bacteria, use is restricted to
treatment of mycobacterial infections and a few other indications.
Rifabutin is well absorbed when taken orally and is distributed widely
in body tissues and fluids, including the CSF. It is metabolized in the
liver and eliminated in bile and, to a much lesser extent, in urine, but
dose adjustments are unnecessary with renal insufficiency. |
| Mechanism of action |
Rifabutin acts via the inhibition of DNA-dependent RNA polymerase
in gram-positive and some gram-negative bacteria, leading to a
suppression of RNA synthesis and cell death. |
| Absorption |
Rifabutin is readily absorbed from the gastrointestinal tract, with an absolute bioavailability averaging 20%. |
| Volume of distribution |
Not Available |
| Protein binding |
85% |
| Metabolism |
Hepatic. Of the five metabolites that have been identified,
25-O-desacetyl and 31-hydroxy are the most predominant. The former
metabolite has an activity equal to the parent drug and contributes up
to 10% to the total antimicrobial activity. |
| Route of elimination |
A mass-balance study in three healthy adult volunteers with
14C-labeled rifabutin showed that 53% of the oral dose was excreted in
the urine, primarily as metabolites. About 30% of the dose is excreted
in the feces. |
| Half life |
45 (± 17) hours |
| Clearance |
|
| Toxicity |
LD50 = 4.8 g/kg (mouse, male) |
