Dose-Ranging Comparison of Rifampin and Rifapentine in Two Pathologically Distinct Murine Models of Tuberculosis
Open Access
- 1 August 2012
- journal article
- research article
- Published by American Society for Microbiology in Antimicrobial Agents and Chemotherapy
- Vol. 56 (8), 4331-4340
- https://doi.org/10.1128/aac.00912-12
Abstract
In previous experiments, replacing the 10-mg/kg of body weight daily dose of rifampin with 7.5 to 10 mg/kg of rifapentine in combinations containing isoniazid and pyrazinamide reduced the duration of treatment needed to cure tuberculosis in BALB/c mice by approximately 50% due to rifapentine's more potent activity and greater drug exposures obtained. In the present study, we performed dose-ranging comparisons of the bactericidal and sterilizing activities of rifampin and rifapentine, alone and in combination with isoniazid and pyrazinamide with or without ethambutol, in BALB/c mice and in C3HeB/FeJ mice, which develop necrotic lung granulomas after infection with Mycobacterium tuberculosis . Each rifamycin demonstrated a significant increase in sterilizing activity with increasing dose. Rifapentine was roughly 4 times more potent in both mouse strains. These results reinforce the rationale for ongoing clinical trials to ascertain the highest well-tolerated doses of rifampin and rifapentine. This study also provides an important benchmark for the efficacy of the first-line regimen in C3HeB/FeJ mice, a strain in which the lung lesions observed after M. tuberculosis infection may better represent the pathology of human tuberculosis.Keywords
This publication has 50 references indexed in Scilit:
- Rifapentine Is Not More Active than Rifampin against Chronic Tuberculosis in Guinea PigsAntimicrobial Agents and Chemotherapy, 2012
- Mouse Model of Necrotic Tuberculosis Granulomas Develops Hypoxic LesionsThe Journal of Infectious Diseases, 2011
- Effects of Tuberculosis, Race, and Human Gene SLCO1B1 Polymorphisms on Rifampin ConcentrationsAntimicrobial Agents and Chemotherapy, 2010
- Noninvasive Pulmonary [ 18 F]-2-Fluoro-Deoxy- d -Glucose Positron Emission Tomography Correlates with Bactericidal Activity of Tuberculosis Drug TreatmentAntimicrobial Agents and Chemotherapy, 2009
- Paradoxical Effect of Isoniazid on the Activity of Rifampin-Pyrazinamide Combination in a Mouse Model of TuberculosisAntimicrobial Agents and Chemotherapy, 2009
- Population Pharmacokinetics of Rifampin in Pulmonary Tuberculosis Patients, Including a Semimechanistic Model To Describe Variable AbsorptionAntimicrobial Agents and Chemotherapy, 2008
- Concentration-Dependent Mycobacterium tuberculosis Killing and Prevention of Resistance by RifampinAntimicrobial Agents and Chemotherapy, 2007
- Early Bactericidal Activity of High-Dose Rifampin in Patients with Pulmonary Tuberculosis Evidenced by Positive Sputum SmearsAntimicrobial Agents and Chemotherapy, 2007
- Pharmacokinetics and Tolerability of a Higher Rifampin Dose versus the Standard Dose in Pulmonary Tuberculosis PatientsAntimicrobial Agents and Chemotherapy, 2007
- Combination Chemotherapy with the Nitroimidazopyran PA-824 and First-Line Drugs in a Murine Model of TuberculosisAntimicrobial Agents and Chemotherapy, 2006