@article{PAR00004147,
  title = {{D}idanosine population pharmacokinetics in {W}est {A}frican human immunodeficiency virus-infected children administered once-daily tablets in relation to efficacy after one year of treatment},
  author = {{H}irt, {D}. and {B}ardin, {C}. and {D}iagbouga, {S}. and {N}acro, {B}. and {H}ien, {H}. and {Z}oure, {E}. and {R}ouet, {F}. and {O}uiminga, {A}. and {U}rien, {S}. and {F}oulongne, {V}. and {V}an de {P}erre, {P}. and {T}r{\'e}luyer, {J}. {M}. and {M}sellati, {P}hilippe},
  editor = {},
  language = {{ENG}},
  abstract = {{O}ur objective was to study didanosine pharmacokinetics in children after the administration of tablets, the only formulation available in {B}urkina {F}aso for which data are missing, and to establish relationships between doses, plasma drug concentrations, and treatment effects (efficacy/toxicity). {D}idanosine concentrations were measured for 40 children after 2 weeks and for 9 children after 2 to 5 months of treatment with a didanosine-lamivudine-efavirenz combination. {A} population pharmacokinetic model was developed with {NONMEM}. {T}he link between the maximal concentration of the drug in plasma ({C}-max), the area under the concentration-time curve ({AUC}), and the decrease in human immunodeficiency virus ({HIV}) type 1 {RNA} levels after 12 months of treatment was evaluated. {T}he threshold {AUC} that improved efficacy was determined by the use of a {W}ilcoxon test for {HIV} {RNA}, and an optimized dosing schedule was simulated. {D}idanosine pharmacokinetics was best described by a one-compartment model with first-order absorption and elimination. {T}he apparent clearance and volume of distribution were higher for tablets, probably due to a lower bioavailability with tablets than with pediatric powder. {T}he decrease in the viral load after 12 months of treatment was significantly correlated with the didanosine {AUC} and {C}-max ({P} <= 0.02) during the first weeks of treatment. {A}n {AUC} of > 0.60 mg/liter . h was significantly linked to a greater decrease in the viral load (a decrease of 3 log(10) versus 2.4 log(10) copies/ml; {P} = 0.03) than that with a lower {AUC}. {A} didanosine dose of 360 mg/m(2) administered as tablets should be a more appropriate dose than 240 mg/m(2) to improve efficacy for these children. {H}owever, data on adverse events with this dosage are missing.},
  keywords = {{BURKINA} {FASO}},
  booktitle = {},
  journal = {{A}ntimicrobial {A}gents and {C}hemotherapy},
  volume = {53},
  numero = {10},
  pages = {4399--4406},
  ISSN = {0066-4804},
  year = {2009},
  DOI = {10.1128/aac.01187-08},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00004147},
}