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Antimicrobial Agents and Chemotherapy, March 2008, p. 852-857, Vol. 52, No. 3
0066-4804/08/$08.00+0     doi:10.1128/AAC.01036-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Population Pharmacokinetics of Levofloxacin, Gatifloxacin, and Moxifloxacin in Adults with Pulmonary Tuberculosis

Infectious Disease Pharmacokinetics Laboratory, National Jewish Medical and Research Center, Denver, Colorado,¹ Schools of Pharmacy and Medicine, University of Colorado, Denver, Colorado,² Núcleo de Doenças Infecciosas, Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Vitória, Brazil,³ Case Western Reserve University School of Medicine and University Hospitals Case Medical Center, Cleveland, Ohio⁴

Received 7 August 2007/ Returned for modification 12 October 2007/ Accepted 20 November 2007

The objective of this study was to determine the population pharmacokinetic parameters of levofloxacin, gatifloxacin, and moxifloxacin following multiple oral doses. Twenty-nine patients with tuberculosis at the University Hospital in Vitória, Brazil, participated. Subjects received multiple doses of one drug (levofloxacin, 1,000 mg daily, or gatifloxacin or moxifloxacin, 400 mg daily) as part of a 7-day study of early bactericidal activity. Serum samples were collected over 24 h after the fifth dose and assayed using validated high-performance liquid chromatography assays. Concentration-time data were analyzed using noncompartmental, compartmental, and population methods. The three drugs were well tolerated. Levofloxacin produced the highest maximum plasma concentrations (median, 15.55 µg/ml; gatifloxacin, 4.75 µg/ml; moxifloxacin, 6.13 µg/ml), largest volume of distribution (median, 81 liters; gatifloxacin, 79 liters; moxifloxacin, 63 liters), and longest elimination half-life (median, 7.4 h; gatifloxacin, 5.0 h; moxifloxacin, 6.5 h). A one-compartment model, with or without weight as a covariate, adequately described the data. Postmodeling simulations using median population parameter estimates closely approximated the median values from the original data. Area under the concentration-time curve/MIC ratios for free drug were high. All three quinolones showed favorable pharmacokinetic and pharmacodynamic indices, with the most favorable results in this population being seen with levofloxacin at the comparative doses used.

Published ahead of print on 10 December 2007.