In:
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Wiley, Vol. 37, No. 9 ( 2017-09), p. 1073-1080
Abstract:
Single nucleotide polymorphisms ( SNP s) in the genes that encode the cytochrome P450 ( CYP ) drug metabolizing enzymes and drug transporters have been reported to influence antiretroviral drug pharmacokinetics. Although primarily metabolized by CYP 2B6 and ‐3A, efavirenz ( EFV ) and lopinavir/ritonavir ( LPV /r) are substrates of P‐glycoprotein and the solute carrier organic ( SLCO ) anion transporter, respectively. We investigated the association between SNP s and efavirenz ( EFV ) or lopinavir/ritonavir ( LPV /r) concentrations in Chinese children infected with the human immunodeficiency virus ( HIV ). Genotyping was performed on CYP 2B6 516G→T, ‐1459C→T, and ‐983T→C, ABCB 1 3435C→T, and SLCO 1B1 521T→C in 229 HIV ‐infected Chinese pediatric patients (age range 4.0 to 17.5 yrs). Plasma concentrations of EFV and LPV /r were measured using validated high‐performance liquid chromatography coupled with the mass spectrum method among 39 and 69 children who received EFV ‐ and LPV /r‐containing regimens, respectively. The frequencies of CYP 2B6 516G→T in the study participants were 71%, 25%, and 4% for the G/G, G/T, and T/T genotypes, respectively. Among the children under therapeutic drug monitoring, 21% and 39% experienced EFV and LPV concentrations, respectively, above the upper threshold of the therapeutic window. CYP 2B6 516G→T was significantly associated with EFV concentrations (p 〈 0.001). Older children (older than 10 yrs) were more likely to have significantly higher EFV concentrations than the younger ones (p=0.0314). CYP 2B6 genotyping and EFV concentration monitoring may help optimize antiretroviral therapy in pediatric patients who initiate an EFV ‐based regimen.
Type of Medium:
Online Resource
ISSN:
0277-0008
,
1875-9114
DOI:
10.1002/phar.2017.37.issue-9
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2061167-5
SSG:
15,3
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