Pharmacokinetics and Metabolism in Drug Design / Methods and Principles in Medicinal Chemistry Bd.51 (PDF)

PHYSICOCHEMISTRY Physicochemistry and Pharmacokinetics Partition and Distribution Coefficients as Measures of Lipophilicity Limitations on the Use of 1-Octanol Further Understanding of logP Alternative Lipophilicity Scales Computational Systems to Determine Lipophilicity Membrane Systems to Study Drug Behavior 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 Intravenous Administration: 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 Factors Governing 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 DISTRIBUTION Membrane Transfer Access to the Target Brain Penetration 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 Symbols Function of Metabolism (Biotransformation) Cytochrome P450 Other Oxidative Metabolism Processes Oxidative Metabolism and Drug Design Nonspecific Esterases Prodrugs to Aid Membrane Transfer Enzymes Catalyzing Drug Conjugation Stability to Conjugation Processes Pharmacodynamics and Conjugation TOXICITY

Dennis Smith worked in the pharmaceutical industry for more than 30 years since gaining his PhD from the University of Manchester (UK). He worked at Pfizer Global R & D at Sandwich for 24 years, with the role of Vice President for Pharmacokinetics, Dynamics and Metabolism. During his career he directly contributed to the Discovery and Development of eight NCEs. Now retired he is still active in an academic
(Visiting Professor, University of Liverpool ) and in an advisory capacity. His research interests and publications span all aspects of drug discovery and development, particularly where drug metabolism impacts on the design of more efficacious and safer drugs.

Charlotte Allerton obtained her first degree in chemistry from the University of Nottingham, and a MPhil in organic chemistry from the University of Cambridge. She joined the Medicinal Chemistry department in Pfizer at Sandwich in 1993 and worked across a range of disease areas, before joining the Pharmacokinetics, Dynamics and Metabolism (PDM) department in 2007. In 2008 Charlotte Allerton became the PDM Sandwich Site Lead.

Amit Kalgutkar received his PhD in organic chemistry from Virginia Polytechnic Institute (USA) and conducted a post-doctoral fellowship at the Department of Biochemistry, Vanderbilt University School of Medicine. He joined Pfizer in 1999, where he is currently a Research Fellow in the Drug Metabolism Group (Groton Laboratories). He is also an adjunct Professor in the Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island.

Han van de Waterbeemd studied physical organic chemistry at the Technical University of Eindhoven and did a PhD in medicinal chemistry at the University of Leiden, The Netherlands. In his pharmaceutical career he worked for Roche, Pfizer and AstraZeneca. His research interests include the role of molecular properties in drug disposition and computational modeling of ADMET properties.

DonWalker obtained a degree in biochemistry

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