Potent twice-weekly rifapentine-containing regimens in murine tuberculosis

Am J Respir Crit Care Med. 2006 Jul 1;174(1):94-101. doi: 10.1164/rccm.200602-280OC. Epub 2006 Mar 30.


Rationale: Recent studies have demonstrated that intermittent administration of rifamycin-based regimens results in higher rates of tuberculosis relapse and treatment failure compared with daily therapy. Twice-weekly treatment with rifampin, isoniazid, and pyrazinamide may be improved by increasing Mycobacterium tuberculosis exposure to rifamycin by substituting rifapentine for rifampin.

Methods: To test this hypothesis, we compared the activities of standard daily and twice-weekly rifampin plus isoniazid-based regimens to those of twice-weekly rifapentine plus isoniazid- or moxifloxacin-containing regimens in the murine model of tuberculosis. Relapse rates were assessed after 4, 5, and 6 mo of treatment to assess stable cure. Single- and multiple-dose pharmacokinetics of rifampin and rifapentine were also determined.

Results: After 2 mo of treatment, twice-weekly therapy with rifapentine (15 or 20 mg/kg), moxifloxacin, and pyrazinamide was significantly more active than standard daily or twice-weekly therapy with rifampin, isoniazid, and pyrazinamide. Stable cure was achieved after 4 mo of twice-weekly rifapentine plus isoniazid- or moxifloxacin-containing therapy, but only after 6 mo of standard daily therapy. Twice-weekly rifapentine (15 mg/kg) displayed more favorable pharmacodynamics than did daily rifampin (10 mg/kg).

Conclusions: By virtue of the enhanced rifamycin exposure, twice-weekly regimens containing rifapentine (15 or 20 mg/kg) may permit shortening the current treatment duration by 2 mo. Such regimens warrant clinical investigation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitubercular Agents / administration & dosage*
  • Antitubercular Agents / pharmacokinetics
  • Aza Compounds / administration & dosage*
  • Aza Compounds / pharmacokinetics
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Fluoroquinolones
  • Isoniazid / administration & dosage*
  • Isoniazid / pharmacokinetics
  • Mice
  • Mice, Inbred BALB C
  • Moxifloxacin
  • Pyrazinamide / administration & dosage*
  • Pyrazinamide / pharmacokinetics
  • Quinolines / administration & dosage*
  • Quinolines / pharmacokinetics
  • Rifampin / administration & dosage*
  • Rifampin / analogs & derivatives*
  • Rifampin / pharmacokinetics
  • Tuberculosis, Pulmonary / drug therapy*
  • Tuberculosis, Pulmonary / metabolism


  • Antitubercular Agents
  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Pyrazinamide
  • Moxifloxacin
  • Isoniazid
  • Rifampin
  • rifapentine