Pharmacokinetics and Metabolism in Drug Design 3e

PHYSICOCHEMISTRY
<br /> Physicochemistry and Pharmacokinetics
<br /> Partition and Distribution Coefficients as Measures of Lipophilicity
<br /> Limitations on the Use of 1–Octanol
<br /> Further Understanding of logP
<br /> Alternative Lipophilicity Scales
<br /> Computational Systems to Determine Lipophilicity
<br /> Membrane Systems to Study Drug Behavior
<br /> Dissolution and Solubility
<br /> The BCS Classification and Central Role of Permeability
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<br /> PHARMACOKINETICS
<br /> Setting the Scene
<br /> Intravenous Administration: Volume of Distribution
<br /> Intravenous Administration: Clearance
<br /> Intravenous Administration: Clearance and Half–life
<br /> Intravenous Administration: Infusion
<br /> Oral Administration
<br /> Repeated Doses
<br /> Development of the Unbound (Free) Drug Model
<br /> Unbound Drug and Drug Action
<br /> Unbound Drug Model and Barriers to Equilibrium
<br /> Pharmacodynamic Models
<br /> Slow Offset Compounds
<br /> Factors Governing Unbound Drug Concentration
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<br /> ABSORPTION
<br /> The Absorption Process
<br /> Dissolution
<br /> Membrane Transfer
<br /> Barriers to Membrane Transfer
<br /> Prodrugs to Increase Oral Absorption
<br /> Active Transport
<br /> Models for Absorption Estimation
<br /> Estimation of Absorption Potential and other Computational
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<br /> DISTRIBUTION
<br /> Membrane Transfer Access to the Target
<br /> Brain Penetration
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<br /> CLEARANCE
<br /> The Clearance Processes
<br /> Role of Transport Proteins in Drug Clearance
<br /> Interplay Between Metabolic and Renal Clearance
<br /> Role of Lipophilicity in Drug Clearance
<br /> Active Metabolites
<br /> Balancing the Rate of Renal and Metabolic clearance and Potency
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<br /> RENAL CLEARANCE
<br /> Kidney Anatomy and Function
<br /> Lipophilicity and Reabsorption by the Kidney
<br /> Effect of Charge on Renal Clearance
<br /> Plasma Protein Binding and Renal Clearance
<br /> Balancing Renal Clearance and Absorption
<br /> Renal Clearance and Drug Design
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<br /> METABOLIC (HEPATIC) CLEARANCE
<br /> Symbols
<br /> Function of Metabolism (Biotransformation)
<br /> Cytochrome P450
<br /> Other Oxidative Metabolism Processes
<br /> Oxidative Metabolism and Drug Design
<br /> Nonspecific Esterases
<br /> Prodrugs to Aid Membrane Transfer
<br /> Enzymes Catalyzing Drug Conjugation
<br /> Stability to Conjugation Processes
<br /> Pharmacodynamics and Conjugation
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<br /> TOXICITY
<br /> Toxicity Findings
<br /> Structure –
<br /> Toxicity Analyses
<br /> Reactive Metabolite Screening in Drug Discovery
<br /> Structural Alerts/Toxicophores in Drug Design
<br /> Dealing with Reactive Metabolite Positives in Drug Discovery: Risk Assessment Strategies –
<br /> Effect of Daily Dose
<br /> Dealing with Reactive Metabolite Positives in Drug Discovery: Risk Assessment Strategies –
<br /> Competing Detoxication Pathways
<br /> Stratification of Toxicity
<br /> Toxicity Prediction: Computational Toxicology
<br /> Toxicogenomics
<br /> Pharmacogenomics
<br /> Enzyme Induction and Drug Design
<br /> Enzyme Inhibition and Drug Design
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<br /> PREDICTING HUMAN PHARMACOKINETICS
<br /> Objectives of Predicting Human Pharmacokinetics
<br /> Allometric Scaling of Preclinical In Vivo PK Parameters
<br /> Prediction of Human PK Parameters Using In Vitro Data
<br /> Elimination Half–Life
<br /> Moving Forward
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<br /> ADME SCREENING
<br /> The High–Throughput Synthesis and Screening Trend
<br /> The Concept of ADME Space
<br /> Drug Metabolism and Discovery Screening Sequences
<br /> Physicochemistry
<br /> Absorption/Permeability
<br /> Metabolism, Induction, and Inhibition
<br /> Transporters
<br /> Protein Binding
<br /> Pharmacokinetics
<br />