EFFECTIVENESS OF RIFAMPIN, RIFABUTIN, AND RIFAPENTINE FOR PREVENTIVE THERAPY OF TUBERCULOSIS IN MICE

To identify alternative regimens for preventive therapy of tuberculosi s, the pharmacokinetics and antimicrobial activities of rifampin (RMP) , rifabutin (RBT), and rifapentine (RPT) were compared in BCG-vaccinat ed and M. tuberculosis-infected immunocompetent mice. RPT showed the h ighest serum peak level (Cmax) and the longest half-life (t(1/2)), whe reas RBT displayed the lowest Cmax and the shortest t(1/2). 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 admin istration was reduced from six to three times weekly, whereas signific ant bactericidal activity was still observed in mice treated with RPT, 10 mg/kg up to once fortnightly, or RBT, 10 mg/kg twice weekly. Becau se the bactericidal activity of RBT, 10 mg/kg six times/wk for 6 wk, o r 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 appropr iate for clinical trials of preventive therapy of tuberculosis.