The Experts below are selected from a list of 126 Experts worldwide ranked by ideXlab platform
Caroline Prouillac - One of the best experts on this subject based on the ideXlab platform.
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Role of ABC transporters in trans-epithelial transport of vitamin K antagonists
Biopharmaceutics & Drug Disposition, 2017Co-Authors: Bernadette Espana, Solange Couturier, Caroline ProuillacAbstract:Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study was to assess, in cell models, the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (Phenindione, fluindione). The results show a basal to apical polarized transport for fluindione, Phenindione and acenocoumarol only. Experimental studies using specific inhibitors of transport protein demonstrate the implication of MRPs and BCRP proteins and to a lesser extent P-gp. Warfarin and acenocoumarol seem to be poor inhibitors of MRPs protein, whereas fluindione and Phenindione have a slight or no effect. The regulation of the expression of ABC transporters by exposure to VKAs was also investigated in Caco-2 cells. The expression of mRNA P-gp, MRP1, MRP2 and BCRP was weakly or not modified after 24 h of VKAs exposure. In conclusion, the intestinal transfer of indanedione derivatives and acenocoumarol could be influenced by transport proteins of the ABC superfamily. Coumarin derivatives are poor inhibitors of these proteins and AVKs have a slight effect on the mRNA ABC transporter expression level. Copyright © 2016 John Wiley & Sons, Ltd.
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Role of ABC transporters in trans-epithelial transport of vitamin K antagonists
Biopharmaceutics and Drug Disposition, 2017Co-Authors: Bernadette Espana, Solange Couturier, Caroline ProuillacAbstract:Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study was to assess, in cell models, the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (Phenindione, fluindione). The results show a basal to apical polarized transport for fluindione, Phenindione and acenocoumarol only. Experimental studies using specific inhibitors of transport protein demonstrate the implication of MRPs and BCRP proteins and to a lesser extent P-gp. Warfarin and acenocoumarol seem to be poor inhibitors of MRPs protein, whereas fluindione and Phenindione have a slight or no effect. The regulation of the expression of ABC transporters by exposure to VKAs was also investigated in Caco-2 cells. The expression of mRNA P-gp, MRP1, MRP2 and BCRP was weakly or not modified after 24h of VKAs exposure. In conclusion, the intestinal transfer of indanedione derivatives and acenocoumarol could be influenced by transport proteins of the ABC superfamily. Coumarin derivatives are poor inhibitors of these proteins and AVKs have a slight effect on the mRNA ABC transporter expression level.
Bernadette Espana - One of the best experts on this subject based on the ideXlab platform.
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Role of ABC transporters in trans-epithelial transport of vitamin K antagonists
Biopharmaceutics & Drug Disposition, 2017Co-Authors: Bernadette Espana, Solange Couturier, Caroline ProuillacAbstract:Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study was to assess, in cell models, the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (Phenindione, fluindione). The results show a basal to apical polarized transport for fluindione, Phenindione and acenocoumarol only. Experimental studies using specific inhibitors of transport protein demonstrate the implication of MRPs and BCRP proteins and to a lesser extent P-gp. Warfarin and acenocoumarol seem to be poor inhibitors of MRPs protein, whereas fluindione and Phenindione have a slight or no effect. The regulation of the expression of ABC transporters by exposure to VKAs was also investigated in Caco-2 cells. The expression of mRNA P-gp, MRP1, MRP2 and BCRP was weakly or not modified after 24 h of VKAs exposure. In conclusion, the intestinal transfer of indanedione derivatives and acenocoumarol could be influenced by transport proteins of the ABC superfamily. Coumarin derivatives are poor inhibitors of these proteins and AVKs have a slight effect on the mRNA ABC transporter expression level. Copyright © 2016 John Wiley & Sons, Ltd.
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Role of ABC transporters in trans-epithelial transport of vitamin K antagonists
Biopharmaceutics and Drug Disposition, 2017Co-Authors: Bernadette Espana, Solange Couturier, Caroline ProuillacAbstract:Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study was to assess, in cell models, the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (Phenindione, fluindione). The results show a basal to apical polarized transport for fluindione, Phenindione and acenocoumarol only. Experimental studies using specific inhibitors of transport protein demonstrate the implication of MRPs and BCRP proteins and to a lesser extent P-gp. Warfarin and acenocoumarol seem to be poor inhibitors of MRPs protein, whereas fluindione and Phenindione have a slight or no effect. The regulation of the expression of ABC transporters by exposure to VKAs was also investigated in Caco-2 cells. The expression of mRNA P-gp, MRP1, MRP2 and BCRP was weakly or not modified after 24h of VKAs exposure. In conclusion, the intestinal transfer of indanedione derivatives and acenocoumarol could be influenced by transport proteins of the ABC superfamily. Coumarin derivatives are poor inhibitors of these proteins and AVKs have a slight effect on the mRNA ABC transporter expression level.
Solange Couturier - One of the best experts on this subject based on the ideXlab platform.
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Role of ABC transporters in trans-epithelial transport of vitamin K antagonists
Biopharmaceutics & Drug Disposition, 2017Co-Authors: Bernadette Espana, Solange Couturier, Caroline ProuillacAbstract:Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study was to assess, in cell models, the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (Phenindione, fluindione). The results show a basal to apical polarized transport for fluindione, Phenindione and acenocoumarol only. Experimental studies using specific inhibitors of transport protein demonstrate the implication of MRPs and BCRP proteins and to a lesser extent P-gp. Warfarin and acenocoumarol seem to be poor inhibitors of MRPs protein, whereas fluindione and Phenindione have a slight or no effect. The regulation of the expression of ABC transporters by exposure to VKAs was also investigated in Caco-2 cells. The expression of mRNA P-gp, MRP1, MRP2 and BCRP was weakly or not modified after 24 h of VKAs exposure. In conclusion, the intestinal transfer of indanedione derivatives and acenocoumarol could be influenced by transport proteins of the ABC superfamily. Coumarin derivatives are poor inhibitors of these proteins and AVKs have a slight effect on the mRNA ABC transporter expression level. Copyright © 2016 John Wiley & Sons, Ltd.
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Role of ABC transporters in trans-epithelial transport of vitamin K antagonists
Biopharmaceutics and Drug Disposition, 2017Co-Authors: Bernadette Espana, Solange Couturier, Caroline ProuillacAbstract:Vitamin K antagonists (VKAs) remain the oral anticoagulant of choice in venous thromboembolic disease. These drugs are characterized by a large inter-individual variability requiring frequent dose tailoring. Genetic polymorphisms for cytochrome CYP2C9 and VKORC1 explain some of the variability, especially in warfarin and acenocoumarol responses. The aim of this study was to assess, in cell models, the role of ABC transporters in the intestinal transfer of the main coumarin derivatives (warfarin, acenocoumarol) and indanedione derivatives (Phenindione, fluindione). The results show a basal to apical polarized transport for fluindione, Phenindione and acenocoumarol only. Experimental studies using specific inhibitors of transport protein demonstrate the implication of MRPs and BCRP proteins and to a lesser extent P-gp. Warfarin and acenocoumarol seem to be poor inhibitors of MRPs protein, whereas fluindione and Phenindione have a slight or no effect. The regulation of the expression of ABC transporters by exposure to VKAs was also investigated in Caco-2 cells. The expression of mRNA P-gp, MRP1, MRP2 and BCRP was weakly or not modified after 24h of VKAs exposure. In conclusion, the intestinal transfer of indanedione derivatives and acenocoumarol could be influenced by transport proteins of the ABC superfamily. Coumarin derivatives are poor inhibitors of these proteins and AVKs have a slight effect on the mRNA ABC transporter expression level.
Mark Sigalov - One of the best experts on this subject based on the ideXlab platform.
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Keto-enol tautomerism of Phenindione and its derivatives: an NMR and density functional theory (DFT) reinvestigation.
The journal of physical chemistry. A, 2015Co-Authors: Mark SigalovAbstract:Keto–enol tautomerism of Phenindione (2-phenyl-1,3-indandione) and of its 4-phenyl-substituted derivatives was reinvestigated by NMR, supported by density functional theory (DFT) quantum-mechanical calculations. The calculated data quantitatively confirmed the stabilization in DMSO solution of the enol form by a strong hydrogen bond. The symmetry of the NMR spectra of the enol forms was explained by a fast proton transfer between carbonyl oxygen atoms, which is facilitated by the formation of a strong ionic complex of the enol form and an anion. It was shown that keto–enol tautomerization also proceeds with the participation of a similar complex between an anion and the diketo form of 2-phenyl-1,3-indandione.
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Keto–Enol Tautomerism of Phenindione and Its Derivatives: An NMR and Density Functional Theory (DFT) Reinvestigation
2015Co-Authors: Mark SigalovAbstract:Keto–enol tautomerism of Phenindione (2-phenyl-1,3-indandione) and of its 4-phenyl-substituted derivatives was reinvestigated by NMR, supported by density functional theory (DFT) quantum-mechanical calculations. The calculated data quantitatively confirmed the stabilization in DMSO solution of the enol form by a strong hydrogen bond. The symmetry of the NMR spectra of the enol forms was explained by a fast proton transfer between carbonyl oxygen atoms, which is facilitated by the formation of a strong ionic complex of the enol form and an anion. It was shown that keto–enol tautomerization also proceeds with the participation of a similar complex between an anion and the diketo form of 2-phenyl-1,3-indandione
B. Kevin Park - One of the best experts on this subject based on the ideXlab platform.
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Characterization of the T-Cell Response in a Patient with Phenindione Hypersensitivity
The Journal of pharmacology and experimental therapeutics, 2005Co-Authors: Dean J. Naisbitt, John Farrell, Peter J. Chamberlain, Josephine E. Hopkins, Neil G. Berry, Munir Pirmohamed, B. Kevin ParkAbstract:The oral anticoagulant Phenindione [2-phenyl-1 H -indene-1,3(2 H )-dione] is associated with hypersensitivity reactions in 1.5 to 3% of patients, the pathogenesis of which is unclear. We describe a patient who developed a severe hypersensitivity reaction that involved both the skin and lungs. A lymphocyte transformation test showed proliferation of T-cells from the hypersensitive patient, but not from four controls on exposure to Phenindione in vitro. Drug-specific T-cell clones were generated and characterized in terms of their phenotype, functionality, and mechanism of antigen presentation. Forty-three human leukocyte antigen class II restricted CD4 + αβ T-cell clones were identified. T-cell activation resulted in the secretion of interferon-γ and interleukin-5. Five of seven clones proliferated with Phenindione alone, whereas two clones also proliferated with 2-phenylindene. Certain T-cell clones were also stimulated by R - and S -warfarin; computer modeling revealed that warfarin can adopt a Phenindione-like structure. Phenindione was presented to T-cells via two pathways: first, bound directly to major histocompatibility complex and second, bound to a processed peptide. Our data show that CD4 + T-cells are involved in the pathophysiology of Phenindione hypersensitivity. There may be cross-sensitivity with warfarin in some Phenindione hypersensitive patients.