Model-Based Efficacy and Toxicity Comparisons of Moxifloxacin for Multidrug-Resistant Tuberculosis

Hwi Yeol Yun, Vincent Chang, Kendra K. Radtke, Qianwen Wang, Natasha Strydom, Min Jung Chang, Radojka M. Savic

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7 Citations (Scopus)

Abstract

Background: Moxifloxacin (MOX) is used as a first-choice drug to treat multidrug-resistant tuberculosis (MDR-TB); however, evidence-based dosing optimization should be strengthened by integrative analysis. The primary goal of this study was to evaluate MOX efficacy and toxicity using integrative model-based approaches in MDR-TB patients. Methods: In total, 113 MDR-TB patients from 5 different clinical trials were analyzed for the development of a population pharmacokinetics (PK) model. A final population PK model was merged with a previously developed lung-lesion distribution and QT prolongation model. Monte Carlo simulation was used to calculate the probability target attainment value based on concentration. An area under the concentration-time curve (AUC)-based target was identified as the minimum inhibitory concentration (MIC) of MOX isolated from MDR-TB patients. Results: The presence of human immunodeficiency virus (HIV) increased clearance by 32.7% and decreased the AUC by 27.4%, compared with HIV-negative MDR-TB patients. A daily dose of 800 mg or a 400-mg, twice-daily dose of MOX is expected to be effective in MDR-TB patients with an MIC of ≤0.25 μg/mL, regardless of PK differences resulting from the presence of HIV. The effect of MOX in HIV-positive MDR-TB patients tended to be decreased dramatically from 0.5 μg/mL, in contrast to the findings in HIV-negative patients. A regimen of twice-daily doses of 400 mg should be considered safer than an 800-mg once-daily dosing regimen, because of the narrow fluctuation of concentrations. Conclusions: Our results suggest that a 400-mg, twice-daily dose of MOX is an optimal dosing regimen for MDR-TB patients because it provides superior efficacy and safety.

Original languageEnglish
Article numberofab660
JournalOpen Forum Infectious Diseases
Volume9
Issue number3
DOIs
Publication statusPublished - 2022 Mar 1

Bibliographical note

Publisher Copyright:
© 2021 The Author(s) 2021. Published by Oxford University Press on behalf of Infectious Diseases Society of America.

All Science Journal Classification (ASJC) codes

  • Infectious Diseases
  • Oncology

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