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To identify alternative regimens for preventive therapy of tuberculosis, the pharmacokinetics and antimicrobial activities of rifampin (RMP), rifabutin (RBT), and rifapentine (RPT) were compared in BCG-vaccinated and M. tuberculosis-infected immunocompetent mice. RPT showed the highest serum peak level (Cmax) and the longest half-life (t1/2), whereas RBT displayed the lowest Cmax and the shortest t1/2. On weight-to-weight basis, both RPT and RBT were more bactericidal than RMP. The activity of RMP was significantly reduced when the frequency of administration was reduced from six to three times weekly, whereas significant bactericidal activity was still observed in mice treated with RPT, 10 mg/kg up to once fortnightly, or RBT, 10 mg/kg twice weekly. Because the bactericidal activity of RBT, 10 mg/kg six times/wk for 6 wk, or RPT, 10 mg/kg two times/wk for 12 wk, was comparable to that of RMP, 10 mg/kg six times/wk for 12 wk in mice, the two regimens are appropriate for clinical trials of preventive therapy of tuberculosis.

Original publication

DOI

10.1164/ajrccm/148.6_pt_1.1541

Type

Journal

The American review of respiratory disease

Publication Date

12/1993

Volume

148

Pages

1541 - 1546

Addresses

Faculté de Médecine Pitié-Salpêtrière, Paris, France.

Keywords

Spleen, Animals, Mice, Mycobacterium tuberculosis, Tuberculosis, Rifabutin, Rifampin, BCG Vaccine, Antitubercular Agents, Colony Count, Microbial, Female