Impact of pharmacogenetics and pregnancy on tenofovir and emtricitabine pharmacokinetics

Gini, Joshua, Olagunju, Adeniyi ORCID: 0000-0002-6588-5749, Dickinson, Laura ORCID: 0000-0001-5557-9396, Waitt, Catriona ORCID: 0000-0003-0134-5855, Neary, Megan ORCID: 0000-0002-4960-2139, Else, Laura J, Siccardi, Marco ORCID: 0000-0002-3539-7867 and Khoo, Saye ORCID: 0000-0002-2769-0967
(2019) Impact of pharmacogenetics and pregnancy on tenofovir and emtricitabine pharmacokinetics. PHARMACOGENOMICS, 20 (4). pp. 217-224.

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<h4>Aim</h4>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.<h4>Method</h4>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.<h4>Results</h4>Pregnancy decreases TFV plasma concentration by 26% (log<sub>10</sub> 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.<h4>Conclusion</h4>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.

Item Type: Article
Uncontrolled Keywords: emtricitabine, pharmacogenetics, pharmacokinetics, postpartum, pregnancy, tenofovir
Depositing User: Symplectic Admin
Date Deposited: 04 Mar 2020 08:20
Last Modified: 19 Jan 2023 00:54
DOI: 10.2217/pgs-2018-0111
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