Present status of tuberculosis: Introduction to rifapentine

Rifapentine is a rifamycin derivative which has a similar profile of microbiological activity to rifampin (rifampicin). The relative bioavailability after a single 600 mg dose in healthy adult volunteers was 70%. Maximum concentrations were achieved from 5-6 h after administration. When oral doses of rifapentine were administered once daily or once every 72 h to healthy volunteers for 10 days, values suggested no significant autoinduction effect on steady-state pharmacokinetics of rifapentine. Rifapentine inhibits DNA-dependent RNA polymerase in susceptible strains of Mycobacterium tuberculosis but not in mammalian cells. At therapeutic levels, rifapentine exhibits bactericidal activity against both intracellular and extracellular M. tuberculosis organisms. Both rifapentine and the 25-desacetyl metabolite accumulate in human monocyte-derived macrophages with intracellular/extracellular ratios of approximately 24:1 and 7:1, respectively. In the treatment of tuberculosis, a small number of resistant cells present within large populations of susceptible cells can rapidly become predominant. Rifapentine resistance development in M. tuberculosis strains is principally due to one of several single point mutations that occur in the rpoB portion of the gene coding for the P-subunit of DNA-dependent RNA polymerase. Due to the potential for resistance development to rifapentine, appropriate susceptibility tests should be performed in the event of persistently positive cultures. M. tuberculosis organisms resistant to other rifamycins are likely to be resistant to rifapentine. A high level of cross-resistance between rifampin and rifapentine has been demonstrated with M. tuberculosis strains. Cross-resistance does not appear between rifapentine and non-rifamycin antimycobacterial agents such as isoniazid and streptomycin. Rifapentine and its 25-desacetyl metabolite have demonstrated in vitro activity against rifamycin-susceptible strains of M. tuberculosis, including bactericidal activity against phagocytized M. tuberculosis organisms grown in activated human macrophages. (C) 1999 Prous Science. Ail rights reserved.