@article{fdi:010068102,
  title = {{A} population pharmacokinetic/pharmacodynamic model predicts favorable hdl cholesterol changes over the first 5 years in children treated with current efavirenz-based regimens},
  author = {{H}omkham, {N}. and {C}ressey, {T}. {R}. and {I}ngsrisawang, {L}. and {B}ouazza, {N}. and {N}gampiyaskul, {C}. and {H}ongsiriwon, {S}. and {S}rirojana, {S}. and {K}anjanavanit, {S}. and {B}hakeecheep, {S}. and {L}e {C}oeur, {S}ophie and {S}alvadori, {N}icolas and {T}reluyer, {J}. {M}. and {J}ourdain, {G}onzague and {U}rien, {S}.},
  editor = {},
  language = {{ENG}},
  abstract = {{E}favirenz use is associated with changes in cholesterol concentrations, but it is unclear whether this effect is related to drug concentrations. {U}sing efavirenz and cholesterol plasma concentrations measured in 87 antiretroviral-naive children in {T}hailand, we assessed indirect response models to describe the evolution of high- and low-density lipoprotein ({HDL}, {LDL}) cholesterol concentrations in relation to efavirenz plasma concentrations over time where efavirenz was assumed to either stimulate cholesterol production or inhibit its elimination. {S}imulations of cholesterol evolution for children with different average efavirenz concentrations ({C}-av) according to their assumed status of fast or slow metabolizers of efavirenz were performed. {A}t treatment initiation, children's median (interquartile range, {IQR}) age was 8 years (5 to 10), body mass index z-score 0.01 (-1.05 to 1.44), {HDL} 31 mg/d{L} (24 to 44), and {LDL} 83 mg/d{L} (69 to 100). {M}edian ({IQR}) efavirenz {C}-av was 1.7 mg/{L} (1.3 to 2.1) during the period of observation. {T}he best model describing the evolution of {HDL} and {LDL} cholesterol concentrations over time assumed that efavirenz inhibited their elimination. {HDL} concentrations increase over 5 years, whereas {LDL} concentrations increased only during the first 4 months and then returned to baseline levels afterward. {S}imulations predicted that, after 3 years, {HDL} would increase to 63 mg/d{L} in fast metabolizers and 97 mg/d{L} in slow metabolizers of efavirenz. {T}he population pharmacokinetic-pharmacodynamic ({PK}-{PD}) model shows that favorable {HDL} cholesterol changes can be expected in children with current efavirenz dosing guidelines over 5 years of treatment.},
  keywords = {lipids ; pharmacokinetics ; pharmacodynamics ; efavirenz ; children ; {THAILANDE}},
  booktitle = {},
  journal = {{J}ournal of {C}linical {P}harmacology},
  volume = {56},
  numero = {9},
  pages = {1076--1083},
  ISSN = {0091-2700},
  year = {2016},
  DOI = {10.1002/jcph.701},
  URL = {https://www.documentation.ird.fr/hor/fdi:010068102},
}