2016
DOI: 10.1016/j.dmpk.2016.06.001
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Gene–gene interactions between DRD3, MRP4 and CYP2B6 polymorphisms and its influence on the pharmacokinetic parameters of efavirenz in HIV infected patients

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Cited by 12 publications
(14 citation statements)
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“…The reason for this is that although a synonymous variant has no impact on the primary structure, there is a formal possibility that the polymorphism affects the secondary structure of the mRNA by altering its stability and/or translatability, thus resulting to a diversity in protein expression levels [40]. Consistent with results reported in the literature, individuals with rs1751034 TC genotype in ABCC4 had a lower plasma concentration and exposure of oral compounds than those with TT genotype [39]. The other three mutation sites (rs1189437, rs1151471, and rs4148546) belong to intron variants, and there have been no published studies on the association between drug pharmacokinetics and any of them, as far as we know.…”
Section: Discussionsupporting
confidence: 82%
See 1 more Smart Citation
“…The reason for this is that although a synonymous variant has no impact on the primary structure, there is a formal possibility that the polymorphism affects the secondary structure of the mRNA by altering its stability and/or translatability, thus resulting to a diversity in protein expression levels [40]. Consistent with results reported in the literature, individuals with rs1751034 TC genotype in ABCC4 had a lower plasma concentration and exposure of oral compounds than those with TT genotype [39]. The other three mutation sites (rs1189437, rs1151471, and rs4148546) belong to intron variants, and there have been no published studies on the association between drug pharmacokinetics and any of them, as far as we know.…”
Section: Discussionsupporting
confidence: 82%
“…Among the variants in the MRP4 gene, two SNPs (rs1751034 and rs1189437) had good correlations with the C max and AUC last of both CK and 20(S)-PPD, as well as their ratio. Although the rs1751034 T>C polymorphism is a synonymous variant, Sanchez-Martin et al showed a significant difference between the ABCC4 rs1751034 T>C polymorphism and the pharmacokinetics of a nonnucleoside reverse transcriptase inhibitor, efavirenz [39]. The reason for this is that although a synonymous variant has no impact on the primary structure, there is a formal possibility that the polymorphism affects the secondary structure of the mRNA by altering its stability and/or translatability, thus resulting to a diversity in protein expression levels [40].…”
Section: Discussionmentioning
confidence: 99%
“…10,29,30 ABCC4 polymorphisms (rs1751034 and rs2274407) have been associated with lower and higher maximum plasma efavirenz concentrations, respectively, and ABCG2 rs2231142 has been associated with an increased risk of abnormal dreams with efavirenz. 31,32 Africans are the most genetically diverse population worldwide. 33 South Africa has the world's largest ART programme, with most patients currently receiving efavirenz/tenofovir/emtricitabine.…”
Section: Introductionmentioning
confidence: 99%
“… 9 Increased CYP2B6 (or other hepatic enzyme) activity would explain lower systemic efavirenz exposure with increasing estradiol concentrations. Similarly, efavirenz is a substrate for efflux drug transporter MRP4, 10 , 11 which like CYP2B6 may also be induced by estradiol. Increased expression of efflux drug transporter in the gut epithelium may point to decreased efavirenz absorption and is consistent with our findings of lower efavirenz concentrations with increased estradiol.…”
Section: Discussionmentioning
confidence: 99%