Population pharmacokinetics of levofloxacin, gatifloxacin, and moxifloxacin in adults with pulmonary tuberculosis

Antimicrob Agents Chemother. 2008 Mar;52(3):852-7. doi: 10.1128/AAC.01036-07. Epub 2007 Dec 10.

Abstract

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 microg/ml; gatifloxacin, 4.75 microg/ml; moxifloxacin, 6.13 microg/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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Adult
  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / adverse effects
  • Anti-Bacterial Agents / pharmacokinetics*
  • Anti-Bacterial Agents / pharmacology
  • Area Under Curve
  • Aza Compounds / administration & dosage
  • Aza Compounds / adverse effects
  • Aza Compounds / pharmacokinetics*
  • Aza Compounds / pharmacology
  • Brazil
  • Female
  • Fluoroquinolones / administration & dosage
  • Fluoroquinolones / adverse effects
  • Fluoroquinolones / pharmacokinetics*
  • Fluoroquinolones / pharmacology
  • Gatifloxacin
  • Humans
  • Levofloxacin*
  • Male
  • Microbial Sensitivity Tests
  • Middle Aged
  • Moxifloxacin
  • Mycobacterium tuberculosis / drug effects*
  • Ofloxacin / administration & dosage
  • Ofloxacin / adverse effects
  • Ofloxacin / pharmacokinetics*
  • Ofloxacin / pharmacology
  • Quinolines / administration & dosage
  • Quinolines / adverse effects
  • Quinolines / pharmacokinetics*
  • Quinolines / pharmacology
  • Tuberculosis, Pulmonary / drug therapy
  • Tuberculosis, Pulmonary / microbiology*

Substances

  • Anti-Bacterial Agents
  • Aza Compounds
  • Fluoroquinolones
  • Quinolines
  • Levofloxacin
  • Ofloxacin
  • Gatifloxacin
  • Moxifloxacin