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Role of selected ABC and SLC transporters in transmembrane permeability of maraviroc: effect on transport in placenta
Matiašková, Zuzana ; Čečková, Martina (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and toxikology Student: Zuzana Matiašková Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Role of selected ABC and SLC transporters in transmembrane permeability of maraviroc: effect on transport in placenta Antiretroviral drug maraviroc is an inhibitor of CCR5-trophic HIV virus and belongs to the group of entry inhibitors. Nowadays, maraviroc is administered as part of combination antiretroviral therapy (cART) primarily in adults, children over the age of two and pregnant women to reduce the risk of transmission of HIV to the fetus. The knowledge of interactions of maraviroc with drug transporters in placenta is crucial for optimizing the therapy during pregnancy, both in terms of efficacy and potential adverse effects. Maraviroc is known substrate of ABCB1 transporter, which plays a protective role to the fetus by its efflux activity in the apical membrane of trophoblast. However, the results of recent study employing dually perfused human placenta suggest involvement of other transport mechanisms in the maraviroc transplacental pharmaocokinetics, especially those operating in the opposite direction to ABCB1. The aim of this study was to evaluate in vitro studies whether, besides ABCB1,...
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Role of selected ABC and SLC transporters in transmembrane permeability of maraviroc: effect on transport in placenta
Matiašková, Zuzana ; Čečková, Martina (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and toxikology Student: Zuzana Matiašková Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Role of selected ABC and SLC transporters in transmembrane permeability of maraviroc: effect on transport in placenta Antiretroviral drug maraviroc is an inhibitor of CCR5-trophic HIV virus and belongs to the group of entry inhibitors. Nowadays, maraviroc is administered as part of combination antiretroviral therapy (cART) primarily in adults, children over the age of two and pregnant women to reduce the risk of transmission of HIV to the fetus. The knowledge of interactions of maraviroc with drug transporters in placenta is crucial for optimizing the therapy during pregnancy, both in terms of efficacy and potential adverse effects. Maraviroc is known substrate of ABCB1 transporter, which plays a protective role to the fetus by its efflux activity in the apical membrane of trophoblast. However, the results of recent study employing dually perfused human placenta suggest involvement of other transport mechanisms in the maraviroc transplacental pharmaocokinetics, especially those operating in the opposite direction to ABCB1. The aim of this study was to evaluate in vitro studies whether, besides ABCB1,...
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Role of selected ABC and SLC transporters in transmembrane permeability of maraviroc: effect on transport in placenta
Matiašková, Zuzana ; Čečková, Martina (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and toxikology Student: Zuzana Matiašková Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Role of selected ABC and SLC transporters in transmembrane permeability of maraviroc: effect on transport in placenta Antiretroviral drug maraviroc is an inhibitor of CCR5-trophic HIV virus and belongs to the group of entry inhibitors. Nowadays, maraviroc is administered as part of combination antiretroviral therapy (cART) primarily in adults, children over the age of two and pregnant women to reduce the risk of transmission of HIV to the fetus. The knowledge of interactions of maraviroc with drug transporters in placenta is crucial for optimizing the therapy during pregnancy, both in terms of efficacy and potential adverse effects. Maraviroc is known substrate of ABCB1 transporter, which plays a protective role to the fetus by its efflux activity in the apical membrane of trophoblast. However, the results of recent study employing dually perfused human placenta suggest involvement of other transport mechanisms in the maraviroc transplacental pharmaocokinetics, especially those operating in the opposite direction to ABCB1. The aim of this study was to evaluate in vitro studies whether, besides ABCB1,...
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Role of selected ABC and SLC transporters in transmembrane permeability of maraviroc: effect on transport in placenta
Matiašková, Zuzana ; Čečková, Martina (advisor) ; Vopršalová, Marie (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and toxikology Student: Zuzana Matiašková Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Role of selected ABC and SLC transporters in transmembrane permeability of maraviroc: effect on transport in placenta Antiretroviral drug maraviroc is an inhibitor of CCR5-trophic HIV virus and belongs to the group of entry inhibitors. Nowadays, maraviroc is administered as part of combination antiretroviral therapy (cART) primarily in adults, children over the age of two and pregnant women to reduce the risk of transmission of HIV to the fetus. The knowledge of interactions of maraviroc with drug transporters in placenta is crucial for optimizing the therapy during pregnancy, both in terms of efficacy and potential adverse effects. Maraviroc is known substrate of ABCB1 transporter, which plays a protective role to the fetus by its efflux activity in the apical membrane of trophoblast. However, the results of recent study employing dually perfused human placenta suggest involvement of other transport mechanisms in the maraviroc transplacental pharmaocokinetics, especially those operating in the opposite direction to ABCB1. The aim of this study was to evaluate in vitro studies whether, besides ABCB1,...
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Study on interaction potential of maraviroc with drug transporters ABCB1 and ABCG2
Erbenová, Kateřina ; Čečková, Martina (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Kateřina Erbenová Supervisor: PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Study of interactions antiretroviral drug maraviroc with drug transporters ABCB1 and ABCG2. Maraviroc is inhibitor of CCR5 HIV virus entry into the cells representing one of the important components of antiretroviral therapy. To optimize the treatment strategies and minimize the therapeutic risks of maraviroc-containing combination antiretroviral therapy, it is important to know the interactions of this drug with other antiretrovirals. In particular, interaction on membrane transporters may affect pharmacokinetics and thereby the tissue concentrations of administered drugs, leading to insufficient efficacy of the therapy or increased toxicity. The aim of this study was to experimentally evaluate interaction of maraviroc with the two most important active drug transporters of the ABC transporter superfamily, ABCB1 (P-glycoprotein) and ABCG2 (BCRP). Using in vitro methods employing cell lines we aimed to fulfil two main goals: (1) to evaluate the inhibitory effect of maraviroc on ABCB1 and ABCG2 transporters and (2) to study if any of these transporters could transfer maraviroc as their substrate. The data...
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Study on interaction potential of maraviroc with drug transporters ABCB1 and ABCG2
Erbenová, Kateřina ; Čečková, Martina (advisor) ; Červený, Lukáš (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Kateřina Erbenová Supervisor: PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Study of interactions antiretroviral drug maraviroc with drug transporters ABCB1 and ABCG2. Maraviroc is inhibitor of CCR5 HIV virus entry into the cells representing one of the important components of antiretroviral therapy. To optimize the treatment strategies and minimize the therapeutic risks of maraviroc-containing combination antiretroviral therapy, it is important to know the interactions of this drug with other antiretrovirals. In particular, interaction on membrane transporters may affect pharmacokinetics and thereby the tissue concentrations of administered drugs, leading to insufficient efficacy of the therapy or increased toxicity. The aim of this study was to experimentally evaluate interaction of maraviroc with the two most important active drug transporters of the ABC transporter superfamily, ABCB1 (P-glycoprotein) and ABCG2 (BCRP). Using in vitro methods employing cell lines we aimed to fulfil two main goals: (1) to evaluate the inhibitory effect of maraviroc on ABCB1 and ABCG2 transporters and (2) to study if any of these transporters could transfer maraviroc as their substrate. The data...
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