Rifabutin

Rifabutin (Mycobutin), an antibiotic related to ri-fampin, shares its mechanism of action, that is, inhibition of RNA polymerase. Rifabutin has significant activity in vitro and in vivo against M. avium-intracellular complex (MAC) isolates from both HIV-infected and non-HIV-infected individuals. It has better activity against MAC organisms than rifampin. Rifabutin is active against M. tuberculosis, including some rifampin-resistant strains, such as M. leprae and M. fortuitum. It has a spectrum of activity against gram-positive and gramnegative organisms similar to that of rifampin. The molecular basis for resistance to rifabutin is shared by both rifampin and rifabutin; this explains the virtually complete cross-resistance that occurs between these drugs.

Rifabutin is well absorbed orally, and peak plasma concentrations are reached in 2 to 3 hours. Because of its lipophilicity, rifabutin achieves a 5- to 10-fold higher concentration in tissues than in plasma. The drug has a half-life range of 16 to 96 hours and is eliminated in urine and bile.

Rifabutin appears as effective as rifampin in the treatment of drug-susceptible tuberculosis and is used in the treatment of latent tuberculosis infection either alone or in combination with pyrazinamide. Clinical use of rifabutin has increased in recent years, especially in the treatment of HIV infection. It is a less potent inducer of cytochrome 450 enzymes pathways than ri-fampin and results in less drug interaction with the protease inhibitors and nonnucleoside reverse tran-scriptase inhibitors. Rifabutin is therefore commonly substituted for rifampin in the treatment of tuberculosis in HIV-infected patients. Another important use of ri-fabutin in the HIV-infected population is prevention and treatment of disseminated MAC.

The adverse effects that most frequently result in discontinuation of rifabutin include GI intolerance, rash, and neutropenia. Rifabutin levels will be increased with concurrent administration of fluconazole and clar-ithromycin, resulting in anterior uveitis, polymyalgia syndrome, and a yellowish-tan discoloration of the skin (pseudojaundice). Other adverse reactions are similar to those of rifampin, such as hepatitis, red-orange discoloration of body fluids, and drug interactions due to effects on the hepatic P450 cytochrome enzyme system.

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