The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Eric Bellissant - One of the best experts on this subject based on the ideXlab platform.
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managing drug drug Interaction between ombitasvir paritaprevir ritonavir dasabuvir and mycophenolate mofetil
Therapeutic Drug Monitoring, 2017Co-Authors: Florian Lemaitre, Christelle Boglionekerrien, Marieclemence Verdier, Dominique Guyader, Caroline Jezequel, Camille Tron, Eric BellissantAbstract:No Drug-Drug Interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of Drug-Drug Interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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managing drug drug Interaction between ombitasvir paritaprevir ritonavir dasabuvir and mycophenolate mofetil
Therapeutic Drug Monitoring, 2017Co-Authors: Florian Lemaitre, Christelle Boglionekerrien, Marieclemence Verdier, Dominique Guyader, Caroline Jezequel, Camille Tron, Zeineb Ben Ali, Eric BellissantAbstract:No Drug-Drug Interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of Drug-Drug Interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.
Scott J Grossman - One of the best experts on this subject based on the ideXlab platform.
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in vitro assessment of metabolic drug drug Interaction potential of apixaban through cytochrome p450 phenotyping inhibition and induction studies
Drug Metabolism and Disposition, 2010Co-Authors: Lifei Wang, Donglu Zhang, Nirmala Raghavan, Ming Yao, Charles A Frost, Brad D Maxwell, Shiangyuan Chen, Theunis C Goosen, Griffith W Humphreys, Scott J GrossmanAbstract:Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. The metabolic Drug-Drug Interaction potential of apixaban was evaluated in vitro. The compound did not show cytochrome P450 inhibition (IC(50) values >20 microM) in incubations of human liver microsomes with the probe substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. Apixaban did not show any effect at concentrations up to 20 muM on enzyme activities or mRNA levels of selected P450 enzymes (CYP1A2, 2B6, and 3A4/5) that are sensitive to induction in incubations with primary human hepatocytes. Apixaban showed a slow metabolic turnover in incubations of human liver microsomes with formation of O-demethylation (M2) and hydroxylation products (M4 and M7) as prominent in vitro metabolites. Experiments with human cDNA-expressed P450 enzymes and P450 chemical inhibitors and correlation with P450 activities in individual human liver microsomes demonstrated that the oxidative metabolism of apixaban for formation of all metabolites was predominantly catalyzed by CYP3A4/5 with a minor contribution of CYP1A2 and CYP2J2 for formation of M2. The contribution of CYP2C8, 2C9, and 2C19 to metabolism of apixaban was less significant. In addition, a human absorption, distribution, metabolism, and excretion study showed that more than half of the dose was excreted as unchanged parent (f(m CYP) <0.5), thus significantly reducing the overall metabolic Drug-Drug Interaction potential of apixaban. Together with a low clinical efficacious concentration and multiple clearance pathways, these results demonstrate that the metabolic Drug-Drug Interaction potential between apixaban and coadministered drugs is low.
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in vitro assessment of metabolic drug drug Interaction potential of apixaban through cytochrome p450 phenotyping inhibition and induction studies
Drug Metabolism and Disposition, 2010Co-Authors: Lifei Wang, Donglu Zhang, Nirmala Raghavan, Charles A Frost, Brad D Maxwell, Shiangyuan Chen, Theunis C Goosen, Kan He, Humphreys W Griffith, Scott J GrossmanAbstract:Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. The metabolic Drug-Drug Interaction potential of apixaban was evaluated in vitro. The compound did not show cytochrome P450 inhibition (IC 50 values >20 μM) in incubations of human liver microsomes with the probe substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. Apixaban did not show any effect at concentrations up to 20 μM on enzyme activities or mRNA levels of selected P450 enzymes (CYP1A2, 2B6, and 3A4/5) that are sensitive to induction in incubations with primary human hepatocytes. Apixaban showed a slow metabolic turnover in incubations of human liver microsomes with formation of O -demethylation (M2) and hydroxylation products (M4 and M7) as prominent in vitro metabolites. Experiments with human cDNA-expressed P450 enzymes and P450 chemical inhibitors and correlation with P450 activities in individual human liver microsomes demonstrated that the oxidative metabolism of apixaban for formation of all metabolites was predominantly catalyzed by CYP3A4/5 with a minor contribution of CYP1A2 and CYP2J2 for formation of M2. The contribution of CYP2C8, 2C9, and 2C19 to metabolism of apixaban was less significant. In addition, a human absorption, distribution, metabolism, and excretion study showed that more than half of the dose was excreted as unchanged parent ( f m CYP
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in vitro assessment of metabolic drug drug Interaction potential of apixaban through cytochrome p450 phenotyping inhibition and induction studies
Drug Metabolism and Disposition, 2010Co-Authors: Lifei Wang, Donglu Zhang, Nirmala Raghavan, Ming Yao, Charles A Frost, Brad D Maxwell, Shiangyuan Chen, Theunis C Goosen, Humphreys W Griffith, Scott J GrossmanAbstract:Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. The metabolic Drug-Drug Interaction potential of apixaban was evaluated in vitro. The compound did not show cytochrome P450 inhibition (IC50 values >20 μM) in incubations of human liver microsomes with the probe substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. Apixaban did not show any effect at concentrations up to 20 μM on enzyme activities or mRNA levels of selected P450 enzymes (CYP1A2, 2B6, and 3A4/5) that are sensitive to induction in incubations with primary human hepatocytes. Apixaban showed a slow metabolic turnover in incubations of human liver microsomes with formation of O-demethylation (M2) and hydroxylation products (M4 and M7) as prominent in vitro metabolites. Experiments with human cDNA-expressed P450 enzymes and P450 chemical inhibitors and correlation with P450 activities in individual human liver microsomes demonstrated that the oxidative metabolism of apixaban for formation of all metabolites was predominantly catalyzed by CYP3A4/5 with a minor contribution of CYP1A2 and CYP2J2 for formation of M2. The contribution of CYP2C8, 2C9, and 2C19 to metabolism of apixaban was less significant. In addition, a human absorption, distribution, metabolism, and excretion study showed that more than half of the dose was excreted as unchanged parent (fm CYP
Florian Lemaitre - One of the best experts on this subject based on the ideXlab platform.
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managing drug drug Interaction between ombitasvir paritaprevir ritonavir dasabuvir and mycophenolate mofetil
Therapeutic Drug Monitoring, 2017Co-Authors: Florian Lemaitre, Christelle Boglionekerrien, Marieclemence Verdier, Dominique Guyader, Caroline Jezequel, Camille Tron, Eric BellissantAbstract:No Drug-Drug Interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of Drug-Drug Interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
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managing drug drug Interaction between ombitasvir paritaprevir ritonavir dasabuvir and mycophenolate mofetil
Therapeutic Drug Monitoring, 2017Co-Authors: Florian Lemaitre, Christelle Boglionekerrien, Marieclemence Verdier, Dominique Guyader, Caroline Jezequel, Camille Tron, Zeineb Ben Ali, Eric BellissantAbstract:No Drug-Drug Interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of Drug-Drug Interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.
Lifei Wang - One of the best experts on this subject based on the ideXlab platform.
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in vitro assessment of metabolic drug drug Interaction potential of apixaban through cytochrome p450 phenotyping inhibition and induction studies
Drug Metabolism and Disposition, 2010Co-Authors: Lifei Wang, Donglu Zhang, Nirmala Raghavan, Ming Yao, Charles A Frost, Brad D Maxwell, Shiangyuan Chen, Theunis C Goosen, Griffith W Humphreys, Scott J GrossmanAbstract:Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. The metabolic Drug-Drug Interaction potential of apixaban was evaluated in vitro. The compound did not show cytochrome P450 inhibition (IC(50) values >20 microM) in incubations of human liver microsomes with the probe substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. Apixaban did not show any effect at concentrations up to 20 muM on enzyme activities or mRNA levels of selected P450 enzymes (CYP1A2, 2B6, and 3A4/5) that are sensitive to induction in incubations with primary human hepatocytes. Apixaban showed a slow metabolic turnover in incubations of human liver microsomes with formation of O-demethylation (M2) and hydroxylation products (M4 and M7) as prominent in vitro metabolites. Experiments with human cDNA-expressed P450 enzymes and P450 chemical inhibitors and correlation with P450 activities in individual human liver microsomes demonstrated that the oxidative metabolism of apixaban for formation of all metabolites was predominantly catalyzed by CYP3A4/5 with a minor contribution of CYP1A2 and CYP2J2 for formation of M2. The contribution of CYP2C8, 2C9, and 2C19 to metabolism of apixaban was less significant. In addition, a human absorption, distribution, metabolism, and excretion study showed that more than half of the dose was excreted as unchanged parent (f(m CYP) <0.5), thus significantly reducing the overall metabolic Drug-Drug Interaction potential of apixaban. Together with a low clinical efficacious concentration and multiple clearance pathways, these results demonstrate that the metabolic Drug-Drug Interaction potential between apixaban and coadministered drugs is low.
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in vitro assessment of metabolic drug drug Interaction potential of apixaban through cytochrome p450 phenotyping inhibition and induction studies
Drug Metabolism and Disposition, 2010Co-Authors: Lifei Wang, Donglu Zhang, Nirmala Raghavan, Charles A Frost, Brad D Maxwell, Shiangyuan Chen, Theunis C Goosen, Kan He, Humphreys W Griffith, Scott J GrossmanAbstract:Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. The metabolic Drug-Drug Interaction potential of apixaban was evaluated in vitro. The compound did not show cytochrome P450 inhibition (IC 50 values >20 μM) in incubations of human liver microsomes with the probe substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. Apixaban did not show any effect at concentrations up to 20 μM on enzyme activities or mRNA levels of selected P450 enzymes (CYP1A2, 2B6, and 3A4/5) that are sensitive to induction in incubations with primary human hepatocytes. Apixaban showed a slow metabolic turnover in incubations of human liver microsomes with formation of O -demethylation (M2) and hydroxylation products (M4 and M7) as prominent in vitro metabolites. Experiments with human cDNA-expressed P450 enzymes and P450 chemical inhibitors and correlation with P450 activities in individual human liver microsomes demonstrated that the oxidative metabolism of apixaban for formation of all metabolites was predominantly catalyzed by CYP3A4/5 with a minor contribution of CYP1A2 and CYP2J2 for formation of M2. The contribution of CYP2C8, 2C9, and 2C19 to metabolism of apixaban was less significant. In addition, a human absorption, distribution, metabolism, and excretion study showed that more than half of the dose was excreted as unchanged parent ( f m CYP
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in vitro assessment of metabolic drug drug Interaction potential of apixaban through cytochrome p450 phenotyping inhibition and induction studies
Drug Metabolism and Disposition, 2010Co-Authors: Lifei Wang, Donglu Zhang, Nirmala Raghavan, Ming Yao, Charles A Frost, Brad D Maxwell, Shiangyuan Chen, Theunis C Goosen, Humphreys W Griffith, Scott J GrossmanAbstract:Apixaban is an oral, direct, and highly selective factor Xa inhibitor in late-stage clinical development for the prevention and treatment of thromboembolic diseases. The metabolic Drug-Drug Interaction potential of apixaban was evaluated in vitro. The compound did not show cytochrome P450 inhibition (IC50 values >20 μM) in incubations of human liver microsomes with the probe substrates of CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, or 3A4/5. Apixaban did not show any effect at concentrations up to 20 μM on enzyme activities or mRNA levels of selected P450 enzymes (CYP1A2, 2B6, and 3A4/5) that are sensitive to induction in incubations with primary human hepatocytes. Apixaban showed a slow metabolic turnover in incubations of human liver microsomes with formation of O-demethylation (M2) and hydroxylation products (M4 and M7) as prominent in vitro metabolites. Experiments with human cDNA-expressed P450 enzymes and P450 chemical inhibitors and correlation with P450 activities in individual human liver microsomes demonstrated that the oxidative metabolism of apixaban for formation of all metabolites was predominantly catalyzed by CYP3A4/5 with a minor contribution of CYP1A2 and CYP2J2 for formation of M2. The contribution of CYP2C8, 2C9, and 2C19 to metabolism of apixaban was less significant. In addition, a human absorption, distribution, metabolism, and excretion study showed that more than half of the dose was excreted as unchanged parent (fm CYP
Camille Tron - One of the best experts on this subject based on the ideXlab platform.
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managing drug drug Interaction between ombitasvir paritaprevir ritonavir dasabuvir and mycophenolate mofetil
Therapeutic Drug Monitoring, 2017Co-Authors: Florian Lemaitre, Christelle Boglionekerrien, Marieclemence Verdier, Dominique Guyader, Caroline Jezequel, Camille Tron, Eric BellissantAbstract:No Drug-Drug Interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of Drug-Drug Interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D. Copyright © 2017 Wolters Kluwer Health, Inc. All rights reserved.
-
managing drug drug Interaction between ombitasvir paritaprevir ritonavir dasabuvir and mycophenolate mofetil
Therapeutic Drug Monitoring, 2017Co-Authors: Florian Lemaitre, Christelle Boglionekerrien, Marieclemence Verdier, Dominique Guyader, Caroline Jezequel, Camille Tron, Zeineb Ben Ali, Eric BellissantAbstract:No Drug-Drug Interaction study has been conducted to date for the combination of ombitasvir, paritaprevir/ritonavir, dasabuvir (3D), and mycophenolic acid (MPA). We here report the case of a hepatitis C virus-infected patient treated with 3D and MPA for vasculitis. In light of the threat of Drug-Drug Interaction, the concentration of MPA was measured before, during, and 15 days after the end of the 3D treatment. Similar values were found at all 3 time points, thus indicating that there is probably no need to adapt MPA dosage to 3D.
