TY - JOUR
T1 - Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice
AU - Ji, B.
AU - Truffot-Pernot, C.
AU - Lacroix, C.
AU - Raviglione, M. C.
AU - O'Brien, R. J.
AU - Olliaro, P.
AU - Roscigno, G.
AU - Grosset, J.
PY - 1993
Y1 - 1993
N2 - 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 (t( 1/2 )), whereas 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 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.
AB - 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 (t( 1/2 )), whereas 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 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.
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U2 - 10.1164/ajrccm/148.6_pt_1.1541
DO - 10.1164/ajrccm/148.6_pt_1.1541
M3 - Article
C2 - 8256897
AN - SCOPUS:0027744137
SN - 0003-0805
VL - 148
SP - 1541
EP - 1546
JO - American Review of Respiratory Disease
JF - American Review of Respiratory Disease
IS - 6 I
ER -