Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir.

Zuzana Neumanova; Lukas Cerveny; Susan L Greenwood; Martina Ceckova; Frantisek Staud

doi:10.1016/j.reprotox.2015.07.070

Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir.

Zuzana Neumanova, Lukas Cerveny, Susan L Greenwood, Martina Ceckova, Frantisek Staud

Division of Developmental Biology & Medicine (L5)

Research output: Contribution to journal › Article › peer-review

Abstract

Abacavir is as a frequent part of combination antiretroviral therapy used in pregnant women. The aim of this study was to investigate, using in vitro, in situ and ex vivo experimental approaches, whether the transplacental pharmacokinetics of abacavir is affected by ATP-binding cassette (ABC) efflux transporters functionally expressed in the placenta: P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), multidrug resistance-associated protein 2 (ABCC2) and multidrug resistance-associated protein 5 (ABCC5). In vitro transport assays revealed that abacavir is a substrate of human ABCB1 and ABCG2 transporters but not of ABCC2 or ABCC5. In addition, in situ experiments using dually perfused rat term placenta confirmed interactions of abacavir with placental Abcb1/Abcg2. In contrast, uptake studies in human placental villous fragments did not reveal any interaction of abacavir with efflux transporters suggesting a large contribution of passive diffusion and/or influx mechanisms to net transplacental abacavir transfer.

Original language	English
Journal	Reproductive toxicology (Elmsford, N.Y.)
Volume	57
DOIs	https://doi.org/10.1016/j.reprotox.2015.07.070
Publication status	Published - Nov 2015

Keywords

Abacavir
Breast cancer resistance protein
HIV
Multidrug resistance-associated proteins
P-glycoprotein
Transplacental pharmacokinetics

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.reprotox.2015.07.070

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@article{344afbc4dd4f4f0aa9941880246a2d5c,

title = "Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir.",

abstract = "Abacavir is as a frequent part of combination antiretroviral therapy used in pregnant women. The aim of this study was to investigate, using in vitro, in situ and ex vivo experimental approaches, whether the transplacental pharmacokinetics of abacavir is affected by ATP-binding cassette (ABC) efflux transporters functionally expressed in the placenta: P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), multidrug resistance-associated protein 2 (ABCC2) and multidrug resistance-associated protein 5 (ABCC5). In vitro transport assays revealed that abacavir is a substrate of human ABCB1 and ABCG2 transporters but not of ABCC2 or ABCC5. In addition, in situ experiments using dually perfused rat term placenta confirmed interactions of abacavir with placental Abcb1/Abcg2. In contrast, uptake studies in human placental villous fragments did not reveal any interaction of abacavir with efflux transporters suggesting a large contribution of passive diffusion and/or influx mechanisms to net transplacental abacavir transfer.",

keywords = "Abacavir, Breast cancer resistance protein, HIV, Multidrug resistance-associated proteins, P-glycoprotein, Transplacental pharmacokinetics",

author = "Zuzana Neumanova and Lukas Cerveny and Greenwood, {Susan L} and Martina Ceckova and Frantisek Staud",

year = "2015",

month = nov,

doi = "10.1016/j.reprotox.2015.07.070",

language = "English",

volume = "57",

journal = "Reproductive toxicology (Elmsford, N.Y.)",

issn = "1873-1708",

publisher = "Elsevier BV",

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TY - JOUR

T1 - Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir.

AU - Neumanova, Zuzana

AU - Cerveny, Lukas

AU - Greenwood, Susan L

AU - Ceckova, Martina

AU - Staud, Frantisek

PY - 2015/11

Y1 - 2015/11

N2 - Abacavir is as a frequent part of combination antiretroviral therapy used in pregnant women. The aim of this study was to investigate, using in vitro, in situ and ex vivo experimental approaches, whether the transplacental pharmacokinetics of abacavir is affected by ATP-binding cassette (ABC) efflux transporters functionally expressed in the placenta: P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), multidrug resistance-associated protein 2 (ABCC2) and multidrug resistance-associated protein 5 (ABCC5). In vitro transport assays revealed that abacavir is a substrate of human ABCB1 and ABCG2 transporters but not of ABCC2 or ABCC5. In addition, in situ experiments using dually perfused rat term placenta confirmed interactions of abacavir with placental Abcb1/Abcg2. In contrast, uptake studies in human placental villous fragments did not reveal any interaction of abacavir with efflux transporters suggesting a large contribution of passive diffusion and/or influx mechanisms to net transplacental abacavir transfer.

AB - Abacavir is as a frequent part of combination antiretroviral therapy used in pregnant women. The aim of this study was to investigate, using in vitro, in situ and ex vivo experimental approaches, whether the transplacental pharmacokinetics of abacavir is affected by ATP-binding cassette (ABC) efflux transporters functionally expressed in the placenta: P-glycoprotein (ABCB1), breast cancer resistance protein (ABCG2), multidrug resistance-associated protein 2 (ABCC2) and multidrug resistance-associated protein 5 (ABCC5). In vitro transport assays revealed that abacavir is a substrate of human ABCB1 and ABCG2 transporters but not of ABCC2 or ABCC5. In addition, in situ experiments using dually perfused rat term placenta confirmed interactions of abacavir with placental Abcb1/Abcg2. In contrast, uptake studies in human placental villous fragments did not reveal any interaction of abacavir with efflux transporters suggesting a large contribution of passive diffusion and/or influx mechanisms to net transplacental abacavir transfer.

KW - Abacavir

KW - Breast cancer resistance protein

KW - HIV

KW - Multidrug resistance-associated proteins

KW - P-glycoprotein

KW - Transplacental pharmacokinetics

U2 - 10.1016/j.reprotox.2015.07.070

DO - 10.1016/j.reprotox.2015.07.070

M3 - Article

C2 - 26169552

SN - 1873-1708

VL - 57

JO - Reproductive toxicology (Elmsford, N.Y.)

JF - Reproductive toxicology (Elmsford, N.Y.)

ER -

Effect of drug efflux transporters on placental transport of antiretroviral agent abacavir.

Abstract

Keywords

UN SDGs

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