@article{fdi:010069452,
  title = {{O}ptimization of the strength of the efavirenz/lamivudine/abacavir fixed-dose combination for paediatric patients},
  author = {{B}ouazza, {N}. and {C}ressey, {T}. {R}. and {F}oissac, {F}. and {B}ienczak, {A}. and {D}enti, {P}. and {M}c{I}lleron, {H}. and {B}urger, {D}. and {P}enazzato, {M}. and {L}allemant, {M}arc and {C}apparelli, {E}. {V}. and {T}reluyer, {J}. {M}. and {U}rien, {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {C}hild-friendly, low-cost, solid, oral fixed-dose combinations ({FDC}s) of efavirenz with lamivudine and abacavir are urgently needed to improve clinical management and drug adherence for children. {M}ethods: {D}ata were pooled from several clinical trials and therapeutic drug monitoring datasets from different countries. {T}he number of children/observations was 505/3667 for efavirenz. {P}opulation pharmacokinetic analyses were performed using a non-linear mixed-effects approach. {F}or abacavir and lamivudine, data from 187 and 920 subjects were available (population pharmacokinetic models previously published). {E}favirenz/lamivudine/abacavir {FDC} strength options assessed were ({I}) 150/75/150, ({II}) 120/60/120 and ({III}) 200/100/200 mg. {M}onte {C}arlo simulations of the different {FDC} strengths were performed to determine the optimal dose within each of the {WHO} weight bands based on drug efficacy/safety targets. {R}esults: {T}he probability of being within the target efavirenz concentration range 12 h post-dose (1-4 mg/{L}) varied between 56% and 60%, regardless of {FDC} option. {O}ption {I} provided a best possible balance between efavirenz treatment failure and toxicity risks. {F}or abacavir and lamivudine, simulations showed that for option {I}.75% of subjects were above the efficacy target. {C}onclusions: {A}ccording to simulations, a paediatric efavirenz/lamivudine/abacavir fixed-dose formulation of 150 mg efavirenz, 75 mg lamivudine and 150 mg abacavir provided the most effective and safe concentrations across {WHO} weight bands, with the flexibility of dosage required across the paediatric population.},
  keywords = {{THAILAND}e ; {AFRIQUE} {DU} {SUD} ; {BURKINA} {FASO}},
  booktitle = {},
  journal = {{J}ournal of {A}ntimicrobial {C}hemotherapy},
  volume = {72},
  numero = {2},
  pages = {490--495},
  ISSN = {0305-7453},
  year = {2017},
  DOI = {10.1093/jac/dkw444},
  URL = {https://www.documentation.ird.fr/hor/fdi:010069452},
}