@article{fdi:010065227,
  title = {{E}xposure to total and protein-unbound rifampin is not affected by malnutrition in indonesian tuberculosis patients},
  author = {te {B}rake, {L}. {H}. {M}. and {R}uslami, {R}. and {L}ater-{N}ijland, {H}. and {M}ooren, {F}. and {T}eulen, {M}. and {A}priani, {L}. and {K}oenderink, {J}. {B}. and {R}ussel, {F}. {G}. and {B}urger, {D}. {M}. and {A}lisjahbana, {B}. and {W}ieringa, {F}ranck and van {C}revel, {R}. and {A}arnoutse, {R}. {E}.},
  editor = {},
  language = {{ENG}},
  abstract = {{N}utritional status may have a profound impact on the pharmacokinetics of drugs, yet only few data are available for tuberculosis ({TB}) drugs. {A}s malnutrition occurs frequently among {TB} patients, we assessed the effect of malnutrition on the steady-state pharmacokinetics of total and protein-unbound rifampin during the intensive phase of {TB} treatment. {I}n a descriptive pharmacokinetic study in {B}andung, {I}ndonesia, patients received a fixed standard rifampin dose of 450 mg once daily during the intensive phase of {TB} treatment. {A} full pharmacokinetic curve for rifampin was recorded, and total and unbound concentrations of rifampin were analyzed in all samples. {R}ifampin pharmacokinetic parameters were compared between severely malnourished ({BMI} of <16.0 kg/m(2)), malnourished ({BMI} of <18.5 kg/m(2)), and well-nourished ({BMI} of >= 18.5 kg/m(2)) individuals. {N}o difference in total and protein-unbound pharmacokinetic parameters between severely malnourished (n = 7), malnourished (n = 11), and well-nourished (n = 25) patients could be demonstrated. {I}n addition, no significant correlation between {BMI} and exposure (area under the concentration-time curve from 0 to 24 h [ {AUC}(0-24)] and maximum concentration of drug in serum [{C}-max]) was found. {F}emales had significantly higher total {AUC}(0-24) (geometric mean, 59.2 versus 48.2 h.mg/liter; {P} = 0.02) and higher unbound {AUC}(0-24) (geometric mean, 6.2 versus 4.8 h.mg/liter; {P} = 0.02) than males. {O}verall, a marked 2-fold interindividual variation in the free fraction was observed (7.6 to 15.0%; n = 36). {N}utritional status and {BMI} do not appear to have a major effect on total and protein-unbound pharmacokinetic parameters of rifampin in {I}ndonesian subjects. {T}he large interindividual variability in the free fraction of rifampin suggests that protein-unbound rather than total rifampin concentrations should preferably be used to study exposure-response relationships.},
  keywords = {{INDONESIE}},
  booktitle = {},
  journal = {{A}ntimicrobial {A}gents and {C}hemotherapy},
  volume = {59},
  numero = {6},
  pages = {3233--3239},
  ISSN = {0066-4804},
  year = {2015},
  DOI = {10.1128/aac.03485-14},
  URL = {https://www.documentation.ird.fr/hor/fdi:010065227},
}