|  | Smith, Dennis / Allerton, Charlotte / Kalgutkar, Amit S. / Waterbeemd, Han van de / Walker, Don K.
Pharmacokinetics and Metabolism in Drug Design
Methods and Principles in Medicinal Chemistry
Edited by Mannhold, Raimund / Kubinyi, Hugo / Folkers, Gerd
 3., revised and updated Edition - April 2012
109.- Euro
2012. X, 258 Pages, Hardcover
169 Fig., 23 Tab.
- Monograph -
ISBN 978-3-527-32954-0 - Wiley-VCH, Weinheim
|
Content
Sample Chapter
Index
| Buy now   
E-Books are also available on all known E-Book shops.
|
| Short description
A concise introduction to the parameters and processes governing the absorption, distribution and retention of drug compounds in the body, now expanded to cover prodrugs, antitumor drugs and predictive approaches.
From the contents
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
Toxicity Findings
Structure - Toxicity Analyses
Reactive Metabolite Screening in Drug Discovery
Structural Alerts/Toxicophores in Drug Design
Dealing 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
Toxicogenomics
Pharmacogenomics
Enzyme Induction and Drug Design
Enzyme Inhibition and Drug Design
PREDICTING HUMAN PHARMACOKINETICS
Objectives of Predicting Human Pharmacokinetics
Allometric Scaling of Preclinical In Vivo PK Parameters
Prediction of Human PK Parameters Using In Vitro Data
Elimination Half-Life
Moving Forward
ADME SCREENING
The High-Throughput Synthesis and Screening Trend
The Concept of ADME Space
Drug Metabolism and Discovery Screening Sequences
Physicochemistry
Absorption/Permeability
Metabolism, Induction, and Inhibition
Transporters
Protein Binding
Pharmacokinetics
|
|
|
|
