Titlebook: Enzyme- and Transporter-Based Drug-Drug Interactions; Progress and Future K. Sandy‘Pang ,A. David‘Rodrigues,Raimund M. Peter Book 2010 Spr

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Impact of Nuclear Receptors CAR, PXR, FXR, and VDR, and Their Ligands On Enzymes and Transporterser, PXR, CAR, FXR, and VDR form a core group of nuclear receptors that regulate the expression of a number of important drug-metabolizing enzymes and drug transporters. In this chapter, the molecular determinants of adaptive response to drug exposure are detailed in the context of clinical relevance

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Impact of Physiological Determinants: Flow, Binding, Transporters and Enzymes on Organ and Total Bodl as enzymes on the area under the curve and clearances of drugs and metabolites. Whole body PBPK models were then developed, with the kidney and intestine or the kidney and liver as the organs for excretion and metabolism. From these PBPK models, the influence of flow, binding, transporters, and en

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In Silico Approaches to Predict DDIscomputational tools to study DDIs. This chapter outlines the main methodologies currently applied including QSAR modeling, pharmacophore modeling, docking, and the combination of in silico and experimental approaches. There is an emphasis on cytochrome P450 and how in silico models are used in curre

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In Vitro Techniques to Study Drug–Drug Interactions of Drug Metabolism: Cytochrome P450ke predictions of in vivo drug–drug interactions. The in vitro experimental conduct, choice of probe substrates appropriate for individual P450 enzymes and the importance of nonspecific binding within in vitro systems are discussed. In addition to the inhibitor/inducer properties, the importance of

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In Vitro Techniques to Study Transporter-Based DDI drug transporters in, for instance, the liver and kidney. In drug discovery and development, it therefore has become increasingly important to identify the propensity of drug candidates to cause such interactions, either as a victim or perpetrator. In this chapter, we describe the status of in vitr

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In Vitro Techniques to Study Drug–Drug Interactions Involving Transport: Caco-2 Model for Study of Ptransporter that is constitutively expressed in barrier tissues and excretory organs, and has wide substrate specificity; consequently, it may be responsible for wide-ranging drug–drug interactions (DDIs). This chapter critically evaluates the utility and limitations of Caco-2 cells, a model for hum