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Antimicrob Agents Chemother. 2019 Jun 3. pii: AAC.00199-19. doi: 10.1128/AAC.00199-19. [Epub ahead of print]

Multiple drug transporters contribute to the placental transfer of emtricitabine.

Author information

1
Women's Hospital, School of Medicine, and College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
2
Women's Hospital, School of Medicine, and College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, Zhejiang, China sundongli@zju.edu.cn chzheng@zju.edu.cn.

Abstract

Emtricitabine (FTC) is a first-line antiviral drug recommended for treatment of acquired immune deficiency syndrome during pregnancy. We hypothesized that transporters located in the placenta contribute to FTC transfer across the blood-placenta barrier. BeWo cells, cell models with stable expression of transporter genes, primary human trophoblast cells (PHTCs) and small interfering (si)RNAs were applied to demonstrate which transporters were involved. FTC accumulation in BeWo cells was reduced markedly by inhibitors of equilibrative nucleoside transporters (ENTs), concentrative nucleoside transporters (CNTs), organic cation transporters (OCTs), organic cation/carnitine transporter (OCTN)1, and increased by inhibitors of breast cancer resistance protein (BCRP) and multidrug resistance-associated proteins (MRPs). ENT1, CNT1, OCTN1, MRP1/2/3 and BCRP were found to transport FTC but not ENT2, CNT3, OCTN2 or multidrug resistance protein (MDR)1. FTC accumulation in PHTCs was decreased significantly by inhibitors of ENTs and OCTN1. These results suggest that ENT1, CNT1 and OCTN1 probably contribute to FTC uptake from the maternal circulation to trophoblasts, and that ENT1, CNT1 and MRP1 are likely involved in FTC transport between trophoblasts and fetal blood, whereas BCRP and MRP1/2/3 facilitate FTC transport from trophoblasts to the maternal circulation. Co-existence of tenofovir or efavirenz with FTC in the cell medium did not influence FTC accumulation in BeWo cells or PHTCs.

PMID:
31160284
DOI:
10.1128/AAC.00199-19

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