Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Faculty of Pharmacy, Obafemi Awolowo University Ile-Ife, Osun State, Nigeria.
Pharmacogenomics. 2019 Mar;20(4):217-223. doi: 10.2217/pgs-2018-0111. Epub 2019 Feb 15.
Treatment and prevention of mother-to-child transmission of HIV in pregnancy utilizes tenofovir (TFV) and emtricitabine (FTC) as NRTI backbone in combination with a third agent from a different class. We hypothesized that combined effect of pregnancy and pharmacogenetics significantly changes TFV and FTC pharmacokinetics (PK). Therefore, this study aims to evaluate the role of SNPs of transporters (ABCC2 and ABCC4) on TFV and FTC PK during pregnancy.
61 pregnant or postpartum women on TFV and FTC were selected from a group of pregnant and postpartum Nigerian women and both SNPs and drug levels were evaluated.
Pregnancy decreases TFV plasma concentration by 26% (log β = -0.131 [-0.228, -0.034; p = 0.009] at median [range] time-point postdose 14 [7-18.5h]). FTC concentration in individuals with ABCC2 12:g.154962860T>C TT genotype were one- to twofold higher than heterozygous (CT) and homozygous (CC) women. All other evaluated SNPs were not significant.
Pregnancy decreased TFV concentration and significant relationship was found between FTC and ABCC2 12:g.154962860T>C wild-type allele. However, the interplay between pregnancy and pharmacogenetics on TFV and FTC PK is unclear but require further evaluation.
在妊娠期间，利用替诺福韦（TFV）和恩曲他滨（FTC）作为 NRTI 骨干，联合第三种来自不同类别的药物，来治疗和预防 HIV 母婴传播。我们假设妊娠和药物遗传学的综合作用会显著改变 TFV 和 FTC 的药代动力学（PK）。因此，本研究旨在评估转运体（ABCC2 和 ABCC4）的 SNP 对妊娠期间 TFV 和 FTC PK 的作用。
从一组尼日利亚妊娠和产后妇女中选择了 61 名接受 TFV 和 FTC 治疗的妊娠或产后妇女，并评估了这些妇女的 SNP 和药物水平。
妊娠使 TFV 血浆浓度降低 26%（logβ=-0.131[-0.228，-0.034;p=0.009]，中位数[范围]给药后时间点 14[7-18.5h]）。ABCC2 12：g.154962860T>C TT 基因型个体的 FTC 浓度是杂合子（CT）和纯合子（CC）女性的一到两倍。所有其他评估的 SNP 均不显著。
妊娠降低了 TFV 浓度，并且 FTC 与 ABCC2 12：g.154962860T>C 野生型等位基因之间存在显著关系。然而，妊娠和药物遗传学对 TFV 和 FTC PK 的相互作用尚不清楚，但需要进一步评估。
