Pharmacokinetics and metabolism in drug design

In this new edition of a bestseller, all the contents have been brought up-to-date by addressing current standards and best practices in the assessment andprediction of ADMET properties. New chapters on prodrugs, antitumor drugs andactive metabolites, among other topics, have been added. The authors, all of them employed at Pfizer in the discovery and development of new active substances, 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. They cover everythingfrom the fundamental principles right up to the impact of pharmacokinetic parameters on the discovery of new drugs. 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. INDICE: Physicochemistry Physicochemistry and Pharmacokinetics Partition and Distribution Coefficient as Measures of Lipophilicity Limitations on the Use of 1-Octanol Further Understanding of log P Alternative Lipophilicity ScalesMembrane Systems to Study Drug Behaviour Dissolution and Solubility The BCS Classification and Central Role of Permeability Pharmacokinetics Setting the Scene Intravenous Administration: Volume of Distribution Intravenous Administration: Clearance Intravenous Administration: Clearance and Half-life IntravenousAdministration: Infusion Oral Administration Repeated Doses Development of the Unbound (Free) Drug Model Unbound Drug and Drug Action Unbound Drug Model and Barriers to Equilibrium Pharmacodynamic Models Slow Offset Compounds FactorsGoverning Unbound Drug Concentration Absorption The Absorption Process Dissolution Membrane Transfer Barriers to Membrane Transfer Prodrugs to Increase Oral Absorption Active Transport Models for Absorption Estimation Estimation of Absorption Potential and Other Computational Approaches Distribution Membrane Transfer Access to the Target Brain Penetration Distribution into Tumours Volume of Distribution and Duration Distribution and Tmax Clearance The 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 Design Metabolic (Hepatic) Clearance Function of Metabolism (Biotransformation) Cytochrome P450 Other Oxidative Metabolism Processes Oxidative Metabolism and Drug Design Non-Specific Esterases Prodrugs to Aid Membrane Transfer Enzymes Catalysing Drug Conjugation Stability to Conjugation Processes Pharmacodynamics and Conjugation Toxicity Toxicity Findings Structure Toxicity Analyses Reactive Metabolite Screening in Drug Discovery Structural Alerts. Toxicophores in Drug Design Risk Assessment Strategies ? Effect of Daily Dose Risk Assessment Strategies ? Competing Detoxication Pathways Stratification of Toxicity Toxicity Prediction and Computational Toxicology Toxicogenomics Pharmacogenomics Enzyme Induction and Drug Design Enzyme Inhibition and Drug Design Predicting Human Pharmacokinetics Objectives of Predicting Human Pharmacokinetics Allometric Scalingof Pre-Clinical In Vivo PK parameters Prediction of Human PK Parameters UsingIn Vitro Data Elimination Half-Life High(er) Throughput ADME Studies The High-Throughput Screening (HTS) Trend Drug Metabolism and Discovery Screening Sequences Physicochemistry Absorption/Permeability Pharmacokinetics Metabolism andInhibition The Concept of ADME Space Computational Approaches in PK and Metabolism Outlook

• ISBN: 978-3-527-32954-0
• Editorial: Wiley-VCH
• Encuadernacion: Cartoné
• Páginas: 278
• Fecha Publicación: 22/02/2012
• Nº Volúmenes: 1
• Idioma: Inglés