Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism.

Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. Research Abstract Details 

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Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. Abstract Text:

Akihiko Saitoh,Courtney V Fletcher,Richard Brundage,Carmelita Alvero,Terrence Fenton,Karen Hsia,Stephen A Spector,

BACKGROUND: The CYP2B6-G516T polymorphism has been shown to alter plasma efavirenz (EFV) concentrations in adults. The impact of CYP2B6-G516T polymorphisms on EFV concentrations may be different in children because of differences in liver maturation and drug dosage. METHODS: The CYP2B6-G516T polymorphisms were analyzed in 71 HIV-1-infected children receiving highly active antiretroviral therapy (HAART) containing EFV for >or=6 months. EFV pharmacokinetics, toxicity profiles, and viral resistance data were also evaluated. RESULTS: The median oral clearance (CL/F) rate was significantly lower in children with the CYP2B6-516-T/T genotype (3.0 L/h/m2, n=13) than in children with the G/T genotype (5.7 L/h/m2, n=30; P=0.02) or the G/G genotype (7.0 L/h/m2, n=31; P=0.003). In children with the CYP2B6-516-G/G genotype, which is associated with higher expression of hepatic CYP2B6, the clearance rate was significantly higher in younger children (<5 years of age) than in older children (>or=5 years of age) (9.7 L/h/m2 vs. 6.6 L/h/m2; P=0.03). No association was found between CYP2B6-G516T polymorphisms and virologic or immunologic responses, toxicity, or the development of viral resistance against EFV. CONCLUSIONS: CYP2B6-G516T polymorphisms significantly affect the CL/F rate of EFV in children. Changes in hepatic enzyme activity by age may need to be considered when evaluating the impact of genetic variants on antiretroviral pharmacokinetics in children.

Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. Publishing Authors By Initials

A Saitoh,CV Fletcher,R Brundage,C Alvero,T Fenton,K Hsia,SA Spector,

For similar genetic phenomena: variation (genetics): polymorphism, genetic research abstracts see: genetic phenomena: variation (genetics): polymorphism, genetic research

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Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of acquired immune deficiency syndromes (1

VOLUME: 45

Page Numbers: 280-5

Journal Abbreviation: J. Acquir. Immune Defic. Syndr

ISSN: 1525-4135

DAY: 1

MONTH: Jul

YEAR: 2007

Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 100892005

Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. Keywords Mesh Terms:

KEYWORDS: Polymorphism, Genetic

MESH TERMS: genetics

Chemical & Substance for Abstract: Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism. Information

Substance Name: Oxidoreductases, N-Demethylating

Registry Number: EC 1.5.-

Grant and Affiliation Information for Efavirenz pharmacokinetics in HIV-1-infected children are associated with CYP2B6-G516T polymorphism.

AFFILIATION: Division of Infectious Diseases, Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093-0672, USA. asaitoh@ucsd.edu

Country: United States

AGENCY: United States NIAID

GRANT: AI-41110

ACRONYM: AI

MEDLINETA: J Acquir Immune Defic Syndr

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