Back to Search
Start Over
Meta-analysis of the effect of CYP2B6, CYP2A6, UGT2B7 and CAR polymorphisms on efavirenz plasma concentrations.
- Source :
-
The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2019 Nov 01; Vol. 74 (11), pp. 3281-3290. - Publication Year :
- 2019
-
Abstract
- Background: Efavirenz primary metabolism is catalysed by CYP2B6 with minor involvement of CYP2A6. Subsequently, phase I metabolites are conjugated by UGT2B7, and constitutive androstane receptor (CAR) has been shown to transcriptionally regulate many relevant enzymes and transporters. Several polymorphisms occurring in the genes coding for these proteins have been shown to impact efavirenz pharmacokinetics in some but not all studies.<br />Objectives: A meta-analysis was performed to assess the overall effect of CYP2B6 rs3745274, CYP2A6 (rs28399454, rs8192726 and rs28399433), UGT2B7 (rs28365062 and rs7439366) and NR1I3 (rs2307424 and rs3003596) polymorphisms on mid-dose efavirenz plasma concentrations.<br />Methods: Following a literature review, pharmacokinetic parameters were compiled and a meta-analysis for these variants was performed using Review Manager and OpenMetaAnalyst. A total of 28 studies were included.<br />Results: Unsurprisingly, the analysis confirmed that individuals homozygous for the T allele for CYP2B6 rs3745274 had significantly higher efavirenz concentrations than those homozygous for the G allele [weighted standard mean difference (WSMD) = 2.98; 95% CI 2.19-3.76; P < 0.00001]. A subgroup analysis confirmed ethnic differences in frequency but with a similar effect size in each ethnic group (P = 0.96). Associations with CYP2A6 and UGT2B7 variants were not statistically significant, but T homozygosity for CAR rs2307424 was associated with significantly lower efavirenz concentrations than in C homozygotes (WSMD = -0.32; 95% CI -0.59 to -0.06; P = 0.02).<br />Conclusions: This meta-analysis provides the overall effect size for the impact of CYP2B6 rs3745274 and NR1I3 rs2307424 on efavirenz pharmacokinetics. The analysis also indicates that some previous associations were not significant when interrogated across studies.<br /> (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Alkynes
Anti-HIV Agents blood
Anti-HIV Agents pharmacokinetics
Benzoxazines pharmacokinetics
Constitutive Androstane Receptor
Cyclopropanes
Genetic Variation
HIV Infections drug therapy
HIV Infections ethnology
Humans
Polymorphism, Single Nucleotide
Reverse Transcriptase Inhibitors pharmacokinetics
ATPases Associated with Diverse Cellular Activities genetics
Benzoxazines blood
Cytochrome P-450 CYP2A6 genetics
Cytochrome P-450 CYP2B6 genetics
Glucuronosyltransferase genetics
Metalloendopeptidases genetics
Reverse Transcriptase Inhibitors blood
Subjects
Details
- Language :
- English
- ISSN :
- 1460-2091
- Volume :
- 74
- Issue :
- 11
- Database :
- MEDLINE
- Journal :
- The Journal of antimicrobial chemotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 31369088
- Full Text :
- https://doi.org/10.1093/jac/dkz329