Plasma efavirenz concentrations and the association with CYP2B6-516G>T polymorphism in HIV-infected Thai Children

Background: Concerns have been raised about the possibility of subtherapeutic efavirenz (EFV) plasma levels in children with the current dosing guideline. Single nucleotide polymorphisms of the hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene have been associated with high interindividual variati...

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Main Authors: Puthanakit T., Tanpaiboom P., Aurpibul L., Cressey T.R., Sirisanthana V.
Format: Article
Language:English
Published: 2014
Online Access:http://www.scopus.com/inward/record.url?eid=2-s2.0-67649177436&partnerID=40&md5=a6c11de0406598bd6fccf9d9cba94e43
http://cmuir.cmu.ac.th/handle/6653943832/2839
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Institution: Chiang Mai University
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spelling th-cmuir.6653943832-28392014-08-30T02:25:27Z Plasma efavirenz concentrations and the association with CYP2B6-516G>T polymorphism in HIV-infected Thai Children Puthanakit T. Tanpaiboom P. Aurpibul L. Cressey T.R. Sirisanthana V. Background: Concerns have been raised about the possibility of subtherapeutic efavirenz (EFV) plasma levels in children with the current dosing guideline. Single nucleotide polymorphisms of the hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene have been associated with high interindividual variations in EFV plasma concentrations. Our objective was to determine the adequacy of EFV dosing and explore the influence of CYP2B6-516G>T polymorphisms on EFV plasma concentrations in Thai HIV-infected children. Methods: A total of 63 HIV-infected children receiving EFV for ≥4 weeks were assessed. Children received EFV daily doses on the basis of body weight bands. Between 12 to 16 h after EFV intake, a blood sample was drawn to measure the EFV plasma concentration and to determine the CYP2B6-516G>T polymorphism using HPLC and direct gene sequencing, respectively. Results: The median age (range) was 12.3 years (3.1-18.7). The mean (±SD) EFV plasma concentration was 3,138 ng/ml (3,313). Eight (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. CYP2B6-516 G/G, G/T and T/T genotypes were found in 48%, 41% and 11% children, respectively. The CYP2B6-516G>T allele frequency was 31.75%. The 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. Conclusions: Current EFV dosing guidelines provide adequate plasma drug concentrations in Thai HIV-infected children. CYP2B6-516G>T polymorphisms significantly affect the drug metabolism of EFV in children. © 2009 International Medical Press. 2014-08-30T02:25:27Z 2014-08-30T02:25:27Z 2009 Article 13596535 19474465 ANTHF http://www.scopus.com/inward/record.url?eid=2-s2.0-67649177436&partnerID=40&md5=a6c11de0406598bd6fccf9d9cba94e43 http://cmuir.cmu.ac.th/handle/6653943832/2839 English
institution Chiang Mai University
building Chiang Mai University Library
country Thailand
collection CMU Intellectual Repository
language English
description Background: Concerns have been raised about the possibility of subtherapeutic efavirenz (EFV) plasma levels in children with the current dosing guideline. Single nucleotide polymorphisms of the hepatic cytochrome P450 isoenzyme 2B6 (CYP2B6) gene have been associated with high interindividual variations in EFV plasma concentrations. Our objective was to determine the adequacy of EFV dosing and explore the influence of CYP2B6-516G>T polymorphisms on EFV plasma concentrations in Thai HIV-infected children. Methods: A total of 63 HIV-infected children receiving EFV for ≥4 weeks were assessed. Children received EFV daily doses on the basis of body weight bands. Between 12 to 16 h after EFV intake, a blood sample was drawn to measure the EFV plasma concentration and to determine the CYP2B6-516G>T polymorphism using HPLC and direct gene sequencing, respectively. Results: The median age (range) was 12.3 years (3.1-18.7). The mean (±SD) EFV plasma concentration was 3,138 ng/ml (3,313). Eight (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. CYP2B6-516 G/G, G/T and T/T genotypes were found in 48%, 41% and 11% children, respectively. The CYP2B6-516G>T allele frequency was 31.75%. The 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. Conclusions: Current EFV dosing guidelines provide adequate plasma drug concentrations in Thai HIV-infected children. CYP2B6-516G>T polymorphisms significantly affect the drug metabolism of EFV in children. © 2009 International Medical Press.
format Article
author Puthanakit T.
Tanpaiboom P.
Aurpibul L.
Cressey T.R.
Sirisanthana V.
spellingShingle Puthanakit T.
Tanpaiboom P.
Aurpibul L.
Cressey T.R.
Sirisanthana V.
Plasma efavirenz concentrations and the association with CYP2B6-516G>T polymorphism in HIV-infected Thai Children
author_facet Puthanakit T.
Tanpaiboom P.
Aurpibul L.
Cressey T.R.
Sirisanthana V.
author_sort Puthanakit T.
title Plasma efavirenz concentrations and the association with CYP2B6-516G>T polymorphism in HIV-infected Thai Children
title_short Plasma efavirenz concentrations and the association with CYP2B6-516G>T polymorphism in HIV-infected Thai Children
title_full Plasma efavirenz concentrations and the association with CYP2B6-516G>T polymorphism in HIV-infected Thai Children
title_fullStr Plasma efavirenz concentrations and the association with CYP2B6-516G>T polymorphism in HIV-infected Thai Children
title_full_unstemmed Plasma efavirenz concentrations and the association with CYP2B6-516G>T polymorphism in HIV-infected Thai Children
title_sort plasma efavirenz concentrations and the association with cyp2b6-516g>t polymorphism in hiv-infected thai children
publishDate 2014
url http://www.scopus.com/inward/record.url?eid=2-s2.0-67649177436&partnerID=40&md5=a6c11de0406598bd6fccf9d9cba94e43
http://cmuir.cmu.ac.th/handle/6653943832/2839
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