@article{PAR00003584,
  title = {{P}lasma efavirenz concentrations and the association with {CYP}2{B}6-516{G} > {T} polymorphism in {HIV}-infected thai children},
  author = {{P}uthanakit, {T}. and {T}anpaiboon, {P}. and {A}urpibul, {L}. and {C}ressey, {T}im and {S}irisanthana, {V}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}ackground: {C}oncerns have been raised about the possibility of subtherapeutic efavirenz ({EFV}) plasma levels in children with the current dosing guideline. {S}ingle nucleotide polymorphisms of the hepatic cytochrome {P}450 isoenzyme 2{B}6 ({CYP}2{B}6) gene have been associated with high inter-individual variations in {EFV} plasma concentrations. {O}ur objective was to determine the adequacy of {EFV} dosing and explore the influence of {CYP}2{B}6-516{G}>{T} polymorphisms on {EFV} plasma concentrations in {T}hai {HIV}-infected children. {M}ethods: {A} total of 63 {HIV}-infected children receiving {EFV} for :4 weeks were assessed. {C}hildren received {EFV} daily doses on the basis of body weight bands. {B}etween 12 to 16 {I}n after {EFV} intake, a blood sample was drawn to measure the {EFV} plasma concentration and to determine the {CYP}2{B}6-516{G}>{T} polymorphism using {HPLC} and direct gene sequencing, respectively. {R}esults: {T}he median age (range) was 12.3 years (3.1-18.7). {T}he mean (+/- {SD}) {EFV} plasma concentration was 3,138 ng/ml (3,313). {E}ight (13%), 45 (71%) and 10 (16%) children had an {EFV} concentration <1,000 ng/ml, 1,000-4,000 ng/ml and >4,000 ng/ml, respectively. {CYP}2{B}6-516 {G}/{G}, {G}/{T} and {T}/{T} genotypes were found in 48%, 41% and 11% children, respectively. {T}he {CYP}2{B}6-5166>{T} allele frequency was 31.75%. {T}he mean (+/- {SD}) {EFV} concentration for children with {G}/{G}, {G}/{T} and {T}/{T} genotypes were 1,604 ng/ml (729), 2,635 ng/ml (1,199) and 11,582 ng/ml (2,972), respectively ({P}<0.001). {A} correlation between {EFV} concentrations >4,000 ng/ml and psychiatric side effects was observed ({P}=0.02), but there was no association with rash, hepatotoxicity or central nervous system disturbances. {C}onclusions: {C}urrent {EFV} dosing guidelines provide adequate plasma drug concentrations in {T}hai {HIV}-infected children. {CYP}2{B}6-516{G}>{T} polymorphisms significantly affect the drug metabolism of {EFV} in children.},
  keywords = {},
  booktitle = {},
  journal = {{A}ntiviral {T}herapy},
  volume = {14},
  numero = {3},
  pages = {315--320},
  ISSN = {1359-6535},
  year = {2009},
  URL = {https://www.documentation.ird.fr/hor/{PAR}00003584},
}