@article{PAR00004148,
  title = {{I}s the recommended dose of efavirenz optimal in young {W}est {A}frican human immunodeficiency virus-infected children ?},
  author = {{H}irt, {D}. and {U}rien, {S}. and {O}livier, {M}. and {P}eyri{\`e}re, {H}. and {N}acro, {B}. and {D}iagbouga, {S}. and {Z}oure, {E}. and {R}ouet, {F}. and {H}ien, {H}. and {M}sellati, {P}hilippe and {V}an de {P}erre, {P}. and {T}r{\'e}luyer, {J}. {M}.},
  editor = {},
  language = {{ENG}},
  abstract = {{W}e aimed in this study to describe efavirenz concentration-time courses in treatment-naive children after once-daily administration to study the effects of age and body weight on efavirenz pharmacokinetics and to test relationships between doses, plasma concentrations, and efficacy. {F}or this purpose, efavirenz concentrations in 48 children were measured after 2 weeks of didanosine-lamivudine-efavirenz treatment, and samples were available for 9/48 children between months 2 and 5 of treatment. {E}favirenz concentrations in 200 plasma specimens were measured using a validated high-performance liquid chromatography method. {A} population pharmacokinetic model was developed with {NONMEM}. {T}he influence of individual characteristics was tested using a likelihood ratio test. {T}he estimated minimal and maximal concentrations of efavirenz in plasma ({C}-min and {C}-max, respectively) and the area under the concentration-time curve ({AUC}) were correlated to the decrease in human immunodeficiency virus type 1 {RNA} levels after 3 months of treatment. {T}he threshold {C}-min (and {AUC}) that improved efficacy was determined. {T}he target minimal concentration of 4 mg/liter was considered for toxicity. {A}n optimized dosing schedule that would place the highest percentage of children in the interval of effective and nontoxic concentrations was simulated. {T}he pharmacokinetics of efavirenz was best described by a one-compartment model with first-order absorption and elimination. {T}he mean apparent clearance and volume of distribution for efavirenz were 0.211 liter/h/kg and 4.48 liters/kg, respectively. {C}learance decreased significantly with age. {W}hen the recommended doses were given to 46 of the 48 children, 19% (44% of children weighing less than 15 kg) had {C}(min)s below 1 mg/liter. {A} significantly higher percentage of children with {C}(min)s of > 1.1 mg/liter or {AUC}s of > 51 mg/liter . h than of children with lower values had viral load decreases greater than 2 log(10) copies/ml after 3 months of treatment. {T}herefore, to optimize the percentage of children with {C}(min)s between 1.1 and 4 mg/liter, children should receive the following once-daily efavirenz doses: 25 mg/kg of body weight from 2 to 6 years, 15 mg/kg from 6 to 10 years, and 10 mg/kg from 10 to 15 years. {T}hese assumptions should be prospectively confirmed.},
  keywords = {{AFRIQUE} {DE} {L}'{OUEST}},
  booktitle = {},
  journal = {{A}ntimicrobial {A}gents and {C}hemotherapy},
  volume = {53},
  numero = {10},
  pages = {4407--4413},
  ISSN = {0066-4804},
  year = {2009},
  DOI = {10.1128/aac.01594-08},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00004148},
}