In this new edition of a bestseller, all the contents have been brought upto-date by addressing current standards and best practices in the assessment and prediction of ADMET properties. Although the previous chapter layout has been retained, substantial revisions have been made, with new topics such as pro-drugs, active metabolites and transporters covered in detail in a manner useful to the Drug Discovery scientist. The authors discuss the parameters and processes important for the absorption, distribution and retention of drug compounds in the body, plus the potential problems created by their transformation into toxic byproducts.While aimed at all those dealing professionally with the development and application of pharmaceutical substances, the readily comprehensible style makes this book equally suitable for students of pharmacy and related subjects. Uniquely comprehensive, the book relates physicochemistry and chemical structure to pharmacokinetic properties and ultimately drug efficacy and safety.

PHYSICOCHEMISTRYPhysicochemistry and PharmacokineticsPartition and Distribution Coefficients as Measures of LipophilicityLimitations on the Use of 1-OctanolFurther Understanding of logPAlternative Lipophilicity ScalesComputational Systems to Determine LipophilicityMembrane Systems to Study Drug Behavior Dissolution and Solubility The BCS Classification and Central Role of Permeability PHARMACOKINETICS Setting the Scene Intravenous Administration: Volume of DistributionIntravenous Administration: Clearance Intravenous Administration: Clearance and Half-life Intravenous Administration: InfusionOral Administration Repeated Doses Development of the Unbound (Free) Drug ModelUnbound Drug and Drug Action Unbound Drug Model and Barriers to Equilibrium Pharmacodynamic Models Slow Offset Compounds Factors Governing Unbound Drug Concentration ABSORPTIONThe Absorption Process Dissolution Membrane Transfer Barriers to Membrane TransferProdrugs to Increase Oral Absorption Active Transport Models for Absorption Estimation Estimation of Absorption Potential and other ComputationalDISTRIBUTION Membrane Transfer Access to the Target Brain Penetration CLEARANCEThe Clearance Processes Role of Transport Proteins in Drug Clearance Interplay Between Metabolic and Renal Clearance Role of Lipophilicity in Drug Clearance Active Metabolites Balancing the Rate of Renal and Metabolic clearance and Potency RENAL CLEARANCE Kidney Anatomy and Function Lipophilicity and Reabsorption by the Kidney Effect of Charge on Renal Clearance Plasma Protein Binding and Renal Clearance Balancing Renal Clearance and Absorption Renal Clearance and Drug DesignMETABOLIC (HEPATIC) CLEARANCE Symbols Function of Metabolism (Biotransformation) Cytochrome P450 Other Oxidative Metabolism Processes Oxidative Metabolism and Drug DesignNonspecific Esterases Prodrugs to Aid Membrane Transfer Enzymes Catalyzing Drug Conjugation Stability to Conjugation Processes Pharmacodynamics and Conjugation TOXICITY Toxicity Findings Structure - Toxicity AnalysesReactive Metabolite Screening in Drug Discovery Structural Alerts/Toxicophores in Drug DesignDealing with Reactive Metabolite Positives in Drug Discovery: Risk Assessment Strategies - Effect of Daily Dose Dealing with Reactive Metabolite Positives in Drug Discovery: Risk Assessment Strategies - Competing Detoxication Pathways Stratification of Toxicity Toxicity Prediction: Computational Toxicology ToxicogenomicsPharmacogenomicsEnzyme Induction and Drug Design Enzyme Inhibition and Drug Design PREDICTING HUMAN PHARMACOKINETICS Objectives of Predicting Human Pharmacokinetics Allometric Scaling of Preclinical In Vivo PK ParametersPrediction of Human PK Parameters Using In Vitro DataElimination Half-LifeMoving Forward ADME SCREENING The High-Throughput Synthesis and Screening TrendThe Concept of ADME Space Drug Metabolism and Discovery Screening SequencesPhysicochemistryAbsorption/PermeabilityMetabolism, Induction, and InhibitionTransportersProtein BindingPharmacokinetics