Increased Doses Lead to Higher Drug Exposures of Levofloxacin for Treatment of Tuberculosis

Abstract

Patients with multidrug-resistant tuberculosis in Peru and South Africa were randomized to a weight-banded nominal dose of 11, 14, 17, or 20 mg/kg/day levofloxacin (minimum, 750 mg) in combination with other second-line agents. A total of 101 patients were included in noncompartmental pharmacokinetic analyses. Respective median areas under the concentration-time curve from 0 to 24 h (AUC0-24) were 109.49, 97.86, 145.33, and 207.04 μg · h/ml. Median maximum plasma concentration (Cmax) were 11.90, 12.02, 14.86, and 19.17 μg/ml, respectively. Higher levofloxacin doses, up to 1,500 mg daily, resulted in higher exposures. (This study has been registered at ClinicalTrials.gov under identifier NCT01918397.).

Keywords: antitubercular agents; levofloxacin; pharmacokinetics; tuberculosis.

Copyright © 2018 American Society for Microbiology.

Figures

FIG 1

Box-and-whisker plot of levofloxacin Cmax (in μg/ml) versus randomized dose (in mg/kg). The ends of the boxes correspond to the 25th and 75th percentiles, respectively, and the middle line corresponds to the median. The diamond center line indicates the means, and the top and bottom of the diamonds show the 95% confidence interv al about the means. Separated circles show statistically significantly different pairs.

FIG 2

Box-and-whisker plot of levofloxacin AUC0–24 (in μg · h/ml) versus randomized dose (in mg/kg). Symbols are as described for Fig. 1.