دورية أكاديمية
أعرض في EDS

Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children in South Africa.

التفاصيل البيبلوغرافية
العنوان: Pharmacogenetics of plasma efavirenz exposure in HIV-infected adults and children in South Africa.
المؤلفون: Sinxadi PZ; Division of Clinical of Pharmacology, Division of Exercise and Endocrine Metabolism, University of Cape Town, Cape Town, South Africa., Leger PD; Vanderbilt University Medical Center, Department of Medicine, Nashville, Tennessee, United States of America., McIlleron HM; Division of Clinical of Pharmacology, Division of Exercise and Endocrine Metabolism, University of Cape Town, Cape Town, South Africa., Smith PJ; Division of Clinical of Pharmacology, Division of Exercise and Endocrine Metabolism, University of Cape Town, Cape Town, South Africa., Dave JA; Division of Exercise and Endocrine Metabolism, Department of Medicine, University of Cape Town, Cape Town, South Africa., Levitt NS; Division of Exercise and Endocrine Metabolism, Department of Medicine, University of Cape Town, Cape Town, South Africa., Maartens G; Division of Clinical of Pharmacology, Division of Exercise and Endocrine Metabolism, University of Cape Town, Cape Town, South Africa., Haas DW; Vanderbilt University School of Medicine, Department of Medicine, Nashville, Tennessee, United States of America.
المصدر: British journal of clinical pharmacology [Br J Clin Pharmacol] 2015 Jul; Vol. 80 (1), pp. 146-56. Date of Electronic Publication: 2015 May 28.
نوع المنشور: Journal Article; Observational Study; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 7503323 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1365-2125 (Electronic) Linking ISSN: 03065251 NLM ISO Abbreviation: Br J Clin Pharmacol Subsets: MEDLINE
أسماء مطبوعة: Publication: Oxford : Wiley-Blackwell
Original Publication: London, Macmillan Journals Ltd.
مواضيع طبية MeSH: Anti-HIV Agents/*blood , Anti-HIV Agents/*pharmacokinetics , Benzoxazines/*blood , Benzoxazines/*pharmacokinetics , Cytochrome P-450 CYP2B6/*genetics , HIV Infections/*genetics, Adolescent ; Adult ; Alkynes ; Anti-HIV Agents/therapeutic use ; Benzoxazines/therapeutic use ; Black People/genetics ; Child ; Child, Preschool ; Constitutive Androstane Receptor ; Cyclopropanes ; Female ; Genotype ; HIV Infections/blood ; HIV Infections/drug therapy ; Humans ; Male ; Middle Aged ; Polymorphism, Single Nucleotide/genetics ; South Africa ; Young Adult
مستخلص: Aims: Genetic factors, notably CYP2B6 516G→T [rs3745274] and 983T→C [rs28399499], explain much of the interindividual variability in efavirenz pharmacokinetics, but data from Africa are limited. We characterized relationships between genetic polymorphisms and plasma efavirenz concentrations in HIV-infected Black South African adults and children.
Methods: Steady-state mid-dosing interval efavirenz concentrations were measured. We genotyped 241 polymorphisms in genes potentially relevant to efavirenz metabolism and transport, including ABCB1, CYP2A6, CYP2B6, CYP3A4, CYP3A5, NR1I2 and NR1I3.
Results: Among 113 participants (59 adults and 54 children), minor allele frequencies for CYP2B6 516G→T, 983T→C, and 15582C→T [rs4803419] were 0.36, 0.07, and 0.09, respectively. Based on composite CYP2B6 15582/516/983 genotype, there were 33 extensive metabolizer, 62 intermediate metabolizer and 18 slow metabolizer genotypes. Median (IQR) mid-dose efavirenz concentrations were 1.44 (1.21-1.93) µg ml(-1), 2.08 (1.68-2.94) µg ml(-1) and 7.26 (4.82-8.34) µg ml(-1) for extensive, intermediate and slow metabolizers, respectively. In univariate analyses, a model that included composite genotype best predicted efavirenz concentrations (β = 0.28, 95% CI 0.21, 0.35, P = 2.4 × 10(-11)). Among individual CYP2B6 polymorphisms, 516G→T best predicted efavirenz concentrations (β = 0.22, 95% CI 0.13, 0.30, P = 1.27 × 10(-6)). There was also associations with 983T→C (β = 0.27, 95% CI 0.10, 0.44, P = 0.002) and 15582C→T (β = 0.11, 95% CI 0.01, 0.22, P = 0.04). Associations were consistent in adults and children. No other polymorphisms were independently associated with efavirenz concentrations.
Conclusions: Composite CYP2B6 genotype based on CYP2B6 516G→T, 983T→C, and 15582C→T best described efavirenz exposure in HIV-infected Black South African adults and children.
(© 2015 The British Pharmacological Society.)
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معلومات مُعتمدة: R01 AI077505 United States AI NIAID NIH HHS; AI-077505 United States AI NIAID NIH HHS; TR-000445 United States TR NCATS NIH HHS; United Kingdom WT_ Wellcome Trust
فهرسة مساهمة: Keywords: CYP2B6; HIV therapy; South Africa; efavirenz; pharmacogenetics
المشرفين على المادة: 0 (Alkynes)
0 (Anti-HIV Agents)
0 (Benzoxazines)
0 (Constitutive Androstane Receptor)
0 (Cyclopropanes)
0 (NR1I3 protein, human)
EC 1.14.14.1 (Cytochrome P-450 CYP2B6)
JE6H2O27P8 (efavirenz)
تواريخ الأحداث: Date Created: 20150123 Date Completed: 20160607 Latest Revision: 20221207
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC4500334
DOI: 10.1111/bcp.12590
PMID: 25611810
قاعدة البيانات: MEDLINE
الوصف
تدمد:1365-2125
DOI:10.1111/bcp.12590