Population pharmacokinetics of levofloxacin, gatifloxacin, and moxifloxacin in adults with pulmonary tuberculosis.
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.
Peloquin
Charles A
CA
Infectious Disease Pharmacokinetics Laboratory, National Jewish Medical and Research Center, Denver, CO 80206, USA. peloquinc@njc.org
Hadad
David Jamil
DJ
Molino
Lucilia Pereira Dutra
LP
Palaci
Moises
M
Boom
W Henry
WH
Dietze
Reynaldo
R
Johnson
John L
JL
D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D019540:Area Under Curve; D001372:Aza Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D001938:Brazil; D005260:Female; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D000077734:Gatifloxacin; D006801:Humans; D064704:Levofloxacin; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D000077266:Moxifloxacin; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D015242:Ofloxacin / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D011804:Quinolines / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics* / Q000494:pharmacology; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology*
D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D064704:Levofloxacin; D015242:Ofloxacin; D000077734:Gatifloxacin; D000077266:Moxifloxacin