Impact of pharmacogenetics and pregnancy on tenofovir and emtricitabine pharmacokinetics. (15th February 2019)

• Record Type: Journal Article
• Authors: Gini, Joshua; Olagunju, Adeniyi; Dickinson, Laura; Waitt, Catriona; Neary, Megan; Else, Laura J; Siccardi, Marco; Khoo, Saye
• Is Part Of: Pharmacogenomics. Volume 20:Number 4(2019)
• Page Start: 217
• Page End: 223
• Publication Date: 2019-02-15
• Subjects: emtricitabine -- pharmacogenetics -- pharmacokinetics -- postpartum -- pregnancy -- tenofovir; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2018-0111
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: 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.Method: 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.Results: Pregnancy decreases TFV plasma concentration by 26% (log10 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.Conclusion: 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.