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Xin Yang - One of the best experts on this subject based on the ideXlab platform.
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pharmacodynamic model of sodium glucose transporter 2 sglt2 inhibition implications for quantitative translational pharmacology
Aaps Journal, 2011Co-Authors: Tristan S Maurer, Carine M Boustanykari, Emi Kimoto, Michael T Leininger, Avijit Ghosh, Nahor Haddishberhane, Aarti Sawantbasak, Meera Tugnait, Xin Yang, Vincent MascittiAbstract:Sodium–glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through increased urinary glucose excretion (UGE). In this study, a biologically based pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was developed. The derived model was used to characterize the acute PK/PD relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative translational pharmacology of dapagliflozin was examined through both prospective simulation and Direct Modeling of mean literature data obtained for dapagliflozin in healthy subjects. Prospective simulations provided time courses of UGE that were of consistent shape to clinical observations, but were modestly biased toward under prediction. Direct Modeling provided an improved characterization of the data and precise parameter estimates which were reasonably consistent with those predicted from preclinical data. Overall, these results indicate that the acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be reasonably well predicted from preclinical data through rational accounting of species differences in pharmacokinetics, physiology, and SGLT2 pharmacology. Because these data can be generated at the earliest stages of drug discovery, the proposed model is useful in the design and development of novel SGLT2 inhibitors. In addition, this model is expected to serve as a useful foundation for future efforts to understand and predict the effects of SGLT2 inhibition under chronic administration and in other patient populations.
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Pharmacodynamic Model of Sodium–Glucose Transporter 2 (SGLT2) Inhibition: Implications for Quantitative Translational Pharmacology
The AAPS journal, 2011Co-Authors: Tristan S Maurer, Michael T Leininger, Avijit Ghosh, Meera Tugnait, Nahor Haddish-berhane, Aarti Sawant-basak, Carine M. Boustany-kari, Li She, Tong Zhu, Xin YangAbstract:Sodium–glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through increased urinary glucose excretion (UGE). In this study, a biologically based pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was developed. The derived model was used to characterize the acute PK/PD relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative translational pharmacology of dapagliflozin was examined through both prospective simulation and Direct Modeling of mean literature data obtained for dapagliflozin in healthy subjects. Prospective simulations provided time courses of UGE that were of consistent shape to clinical observations, but were modestly biased toward under prediction. Direct Modeling provided an improved characterization of the data and precise parameter estimates which were reasonably consistent with those predicted from preclinical data. Overall, these results indicate that the acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be reasonably well predicted from preclinical data through rational accounting of species differences in pharmacokinetics, physiology, and SGLT2 pharmacology. Because these data can be generated at the earliest stages of drug discovery, the proposed model is useful in the design and development of novel SGLT2 inhibitors. In addition, this model is expected to serve as a useful foundation for future efforts to understand and predict the effects of SGLT2 inhibition under chronic administration and in other patient populations.
Tristan S Maurer - One of the best experts on this subject based on the ideXlab platform.
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pharmacodynamic model of sodium glucose transporter 2 sglt2 inhibition implications for quantitative translational pharmacology
Aaps Journal, 2011Co-Authors: Tristan S Maurer, Carine M Boustanykari, Emi Kimoto, Michael T Leininger, Avijit Ghosh, Nahor Haddishberhane, Aarti Sawantbasak, Meera Tugnait, Xin Yang, Vincent MascittiAbstract:Sodium–glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through increased urinary glucose excretion (UGE). In this study, a biologically based pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was developed. The derived model was used to characterize the acute PK/PD relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative translational pharmacology of dapagliflozin was examined through both prospective simulation and Direct Modeling of mean literature data obtained for dapagliflozin in healthy subjects. Prospective simulations provided time courses of UGE that were of consistent shape to clinical observations, but were modestly biased toward under prediction. Direct Modeling provided an improved characterization of the data and precise parameter estimates which were reasonably consistent with those predicted from preclinical data. Overall, these results indicate that the acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be reasonably well predicted from preclinical data through rational accounting of species differences in pharmacokinetics, physiology, and SGLT2 pharmacology. Because these data can be generated at the earliest stages of drug discovery, the proposed model is useful in the design and development of novel SGLT2 inhibitors. In addition, this model is expected to serve as a useful foundation for future efforts to understand and predict the effects of SGLT2 inhibition under chronic administration and in other patient populations.
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Pharmacodynamic Model of Sodium–Glucose Transporter 2 (SGLT2) Inhibition: Implications for Quantitative Translational Pharmacology
The AAPS journal, 2011Co-Authors: Tristan S Maurer, Michael T Leininger, Avijit Ghosh, Meera Tugnait, Nahor Haddish-berhane, Aarti Sawant-basak, Carine M. Boustany-kari, Li She, Tong Zhu, Xin YangAbstract:Sodium–glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through increased urinary glucose excretion (UGE). In this study, a biologically based pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was developed. The derived model was used to characterize the acute PK/PD relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative translational pharmacology of dapagliflozin was examined through both prospective simulation and Direct Modeling of mean literature data obtained for dapagliflozin in healthy subjects. Prospective simulations provided time courses of UGE that were of consistent shape to clinical observations, but were modestly biased toward under prediction. Direct Modeling provided an improved characterization of the data and precise parameter estimates which were reasonably consistent with those predicted from preclinical data. Overall, these results indicate that the acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be reasonably well predicted from preclinical data through rational accounting of species differences in pharmacokinetics, physiology, and SGLT2 pharmacology. Because these data can be generated at the earliest stages of drug discovery, the proposed model is useful in the design and development of novel SGLT2 inhibitors. In addition, this model is expected to serve as a useful foundation for future efforts to understand and predict the effects of SGLT2 inhibition under chronic administration and in other patient populations.
Kun Xu - One of the best experts on this subject based on the ideXlab platform.
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unified gas kinetic scheme for diatomic molecular flow with translational rotational and vibrational modes
Journal of Computational Physics, 2017Co-Authors: Zhao Wang, Qibing Li, Kun XuAbstract:Abstract The unified gas-kinetic scheme (UGKS) is a Direct Modeling method for both continuum and rarefied flow computations. In the previous study, the UGKS was developed for diatomic molecular simulations with translation and rotational motions. In this paper, a UGKS with non-equilibrium translational, rotational, and vibrational degrees of freedom, will be developed. The new scheme is based on the phenomenological gas dynamics model, where the translational, rotational, and vibrational modes get to the equilibrium with different time scales with the introduction of rotational and vibrational collision numbers. This new scheme is tested in a few cases, such as the homogeneous flow relaxation, shock structure, shock tube problem, and flow passing through a circular and semi-circular cylinders. The analytical and DSMC solutions are used for the validation of the UGKS, and reasonable agreements have been achieved.
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unified gas kinetic scheme with multigrid convergence for rarefied flow study
Physics of Fluids, 2017Co-Authors: Chengwen Zhong, Kun XuAbstract:The unified gas kinetic scheme (UGKS) is based on Direct Modeling of gas dynamics on the mesh size and time step scales. With the Modeling of particle transport and collision in a time-dependent flux function in a finite volume framework, the UGKS can connect the flow physics smoothly from the kinetic particle transport to the hydrodynamic wave propagation. In comparison with the Direct simulation Monte Carlo (DSMC) method, the current equation-based UGKS can implement implicit techniques in the updates of macroscopic conservative variables and microscopic distribution functions. The implicit UGKS significantly increases the convergence speed for steady flow computations, especially in the highly rarefied and near continuum regimes. In order to further improve the computational efficiency, for the first time, a geometric multigrid technique is introduced into the implicit UGKS, where the prediction step for the equilibrium state and the evolution step for the distribution function are both treated with mu...
Vincent Mascitti - One of the best experts on this subject based on the ideXlab platform.
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pharmacodynamic model of sodium glucose transporter 2 sglt2 inhibition implications for quantitative translational pharmacology
Aaps Journal, 2011Co-Authors: Tristan S Maurer, Carine M Boustanykari, Emi Kimoto, Michael T Leininger, Avijit Ghosh, Nahor Haddishberhane, Aarti Sawantbasak, Meera Tugnait, Xin Yang, Vincent MascittiAbstract:Sodium–glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through increased urinary glucose excretion (UGE). In this study, a biologically based pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was developed. The derived model was used to characterize the acute PK/PD relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative translational pharmacology of dapagliflozin was examined through both prospective simulation and Direct Modeling of mean literature data obtained for dapagliflozin in healthy subjects. Prospective simulations provided time courses of UGE that were of consistent shape to clinical observations, but were modestly biased toward under prediction. Direct Modeling provided an improved characterization of the data and precise parameter estimates which were reasonably consistent with those predicted from preclinical data. Overall, these results indicate that the acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be reasonably well predicted from preclinical data through rational accounting of species differences in pharmacokinetics, physiology, and SGLT2 pharmacology. Because these data can be generated at the earliest stages of drug discovery, the proposed model is useful in the design and development of novel SGLT2 inhibitors. In addition, this model is expected to serve as a useful foundation for future efforts to understand and predict the effects of SGLT2 inhibition under chronic administration and in other patient populations.
Meera Tugnait - One of the best experts on this subject based on the ideXlab platform.
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pharmacodynamic model of sodium glucose transporter 2 sglt2 inhibition implications for quantitative translational pharmacology
Aaps Journal, 2011Co-Authors: Tristan S Maurer, Carine M Boustanykari, Emi Kimoto, Michael T Leininger, Avijit Ghosh, Nahor Haddishberhane, Aarti Sawantbasak, Meera Tugnait, Xin Yang, Vincent MascittiAbstract:Sodium–glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through increased urinary glucose excretion (UGE). In this study, a biologically based pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was developed. The derived model was used to characterize the acute PK/PD relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative translational pharmacology of dapagliflozin was examined through both prospective simulation and Direct Modeling of mean literature data obtained for dapagliflozin in healthy subjects. Prospective simulations provided time courses of UGE that were of consistent shape to clinical observations, but were modestly biased toward under prediction. Direct Modeling provided an improved characterization of the data and precise parameter estimates which were reasonably consistent with those predicted from preclinical data. Overall, these results indicate that the acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be reasonably well predicted from preclinical data through rational accounting of species differences in pharmacokinetics, physiology, and SGLT2 pharmacology. Because these data can be generated at the earliest stages of drug discovery, the proposed model is useful in the design and development of novel SGLT2 inhibitors. In addition, this model is expected to serve as a useful foundation for future efforts to understand and predict the effects of SGLT2 inhibition under chronic administration and in other patient populations.
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Pharmacodynamic Model of Sodium–Glucose Transporter 2 (SGLT2) Inhibition: Implications for Quantitative Translational Pharmacology
The AAPS journal, 2011Co-Authors: Tristan S Maurer, Michael T Leininger, Avijit Ghosh, Meera Tugnait, Nahor Haddish-berhane, Aarti Sawant-basak, Carine M. Boustany-kari, Li She, Tong Zhu, Xin YangAbstract:Sodium–glucose co-transporter-2 (SGLT2) inhibitors are an emerging class of agents for use in the treatment of type 2 diabetes mellitus (T2DM). Inhibition of SGLT2 leads to improved glycemic control through increased urinary glucose excretion (UGE). In this study, a biologically based pharmacokinetic/pharmacodynamic (PK/PD) model of SGLT2 inhibitor-mediated UGE was developed. The derived model was used to characterize the acute PK/PD relationship of the SGLT2 inhibitor, dapagliflozin, in rats. The quantitative translational pharmacology of dapagliflozin was examined through both prospective simulation and Direct Modeling of mean literature data obtained for dapagliflozin in healthy subjects. Prospective simulations provided time courses of UGE that were of consistent shape to clinical observations, but were modestly biased toward under prediction. Direct Modeling provided an improved characterization of the data and precise parameter estimates which were reasonably consistent with those predicted from preclinical data. Overall, these results indicate that the acute clinical pharmacology of SGLT2 inhibitors in healthy subjects can be reasonably well predicted from preclinical data through rational accounting of species differences in pharmacokinetics, physiology, and SGLT2 pharmacology. Because these data can be generated at the earliest stages of drug discovery, the proposed model is useful in the design and development of novel SGLT2 inhibitors. In addition, this model is expected to serve as a useful foundation for future efforts to understand and predict the effects of SGLT2 inhibition under chronic administration and in other patient populations.