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Am J Respir Crit Care Med. 2006 Jul 1;174(1):94-101. Epub 2006 Mar 30.

Potent twice-weekly rifapentine-containing regimens in murine tuberculosis.

Author information

1
Center for Tuberculosis Research, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.

Abstract

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.

PMID:
16574936
PMCID:
PMC1862756
DOI:
10.1164/rccm.200602-280OC
[Indexed for MEDLINE]
Free PMC Article

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