@article{PAR00010835,
  title = {{E}valuation of initial and steady-state gatifloxacin pharmacokinetics and dose in pulmonary tuberculosis patients by using {M}onte {C}arlo simulations},
  author = {{S}mythe, {W}. and {M}erle, {C}. {S}. and {R}ustomjee, {R}. and {G}ninafon, {M}. and {L}o, {M}. {B}. and {B}ah-{S}ow, {O}. and {O}lliaro, {P}. {L}. and {L}ienhardt, {C}hristian and {H}orton, {J}. and {S}mith, {P}. and {M}c{I}lleron, {H}. and {S}imonsson, {U}. {S}. {H}.},
  editor = {},
  language = {{ENG}},
  abstract = {{A} 4-month regimen of gatifloxacin with rifampin, isoniazid, and pyrazinamide is being evaluated for the treatment of tuberculosis in a phase 3 randomized controlled trial ({OFLOTUB}). {A} prior single-dose study found that gatifloxacin exposure increased by 14% in the combination. {T}he aims of the study are to evaluate the initial and steady-state pharmacokinetics of gatifloxacin when daily doses are given to patients with newly diagnosed drug-sensitive pulmonary tuberculosis as part of a combination regimen and to evaluate the gatifloxacin dose with respect to the probability of attaining a pharmacokinetic/pharmacodynamic target. {W}e describe the population pharmacokinetics of gatifloxacin from the first dose to a median of 28 days in 169 adults enrolled in the {OFLOTUB} trial in {B}enin, {G}uinea, {S}enegal, and {S}outh {A}frica. {T}he probability of achieving a ratio of >= 125 for the area under the concentration time curve to infinity ({AUC}(0-infinity)) for the free fraction of gatifloxacin over the {MIC} (f{AUC}/{MIC}) was investigated using {M}onte {C}arlo simulations. {T}he median {AUC}(0-infinity) of 41.2 mu g.h/ml decreased on average by 14.3% (90% confidence interval [{CI}], -90.5% to +61.5%) following multiple 400-mg daily doses. {A}t steady state, 90% of patients achieved an f{AUC}/{MIC} of >= 125 only when the {MIC} was <0.125 mu g/ml. {W}e conclude that systemic exposure to gatifloxacin declines with repeated daily 400-mg doses when used together with rifampin, isoniazid, and pyrazinamide, thus compensating for any initial increase in gatifloxacin levels due to a drug interaction. ({T}he {OFLOTUB} study has been registered at {C}linical{T}rials.gov under registration no. {NCT}00216385.)},
  keywords = {},
  booktitle = {},
  journal = {{A}ntimicrobial {A}gents and {C}hemotherapy},
  volume = {57},
  numero = {9},
  pages = {4164--4171},
  ISSN = {0066-4804},
  year = {2013},
  DOI = {10.1128/aac.00479-13},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00010835},
}