| Description |
1 online resource (x, 257 pages) : illustrations |
| Series |
Methods and principles in medicinal chemistry ; v. 51 |
|
Methods and principles in medicinal chemistry ; v. 51.
|
| Contents |
Pharmacokinetics and Metabolism in Drug Design; Contents; A Personal Foreword; 1 Physicochemistry; 1.1 Physicochemistry and Pharmacokinetics; 1.2 Partition and Distribution Coefficients as Measures of Lipophilicity; 1.3 Limitations on the Use of 1-Octanol; 1.4 Further Understanding of log P; 1.4.1 Unraveling the Principal Contributions to log P; 1.4.2 Hydrogen Bonding; 1.4.3 Polar Surface Area; 1.4.4 Molecular Size and Shape; 1.5 Alternative Lipophilicity Scales; 1.6 Computational Systems to Determine Lipophilicity; 1.7 Membrane Systems to Study Drug Behavior; 1.8 Dissolution and Solubility |
|
1.9 The BCS Classification and Central Role of PermeabilityReferences; 2 Pharmacokinetics; 2.1 Setting the Scene; 2.2 Intravenous Administration: Volume of Distribution; 2.3 Intravenous Administration: Clearance; 2.4 Intravenous Administration: Clearance and Half-life; 2.5 Intravenous Administration: Infusion; 2.6 Oral Administration; 2.7 Repeated Doses; 2.8 Development of the Unbound (Free) Drug Model; 2.9 Unbound Drug and Drug Action; 2.10 Unbound Drug Model and Barriers to Equilibrium; 2.11 Pharmacodynamic Models; 2.12 Slow Offset Compounds |
|
2.13 Factors Governing Unbound Drug ConcentrationReferences; 3 Absorption; 3.1 The Absorption Process; 3.2 Dissolution; 3.3 Membrane Transfer; 3.4 Barriers to Membrane Transfer; 3.5 Prodrugs to Increase Oral Absorption; 3.6 Active Transport; 3.7 Models for Absorption Estimation; 3.8 Estimation of Absorption Potential and other Computational Approaches; References; 4 Distribution; 4.1 Membrane Transfer Access to the Target; 4.2 Brain Penetration; 4.2.1 Accumulation of Lower Permeability Compounds into the Brain; 4.2.2 Distribution into Tumors; 4.2.3 Volume of Distribution and Duration |
|
4.2.4 Distribution and TmaxReferences; 5 Clearance; 5.1 The Clearance Processes; 5.2 Role of Transport Proteins in Drug Clearance; 5.3 Interplay Between Metabolic and Renal Clearance; 5.4 Role of Lipophilicity in Drug Clearance; 5.5 Active Metabolites; 5.6 Balancing the Rate of Renal and Metabolic clearance and Potency; References; 6 Renal Clearance; 6.1 Kidney Anatomy and Function; 6.2 Lipophilicity and Reabsorption by the Kidney; 6.3 Effect of Charge on Renal Clearance; 6.4 Plasma Protein Binding and Renal Clearance; 6.5 Balancing Renal Clearance and Absorption |
|
6.6 Renal Clearance and Drug DesignReferences; 7 Metabolic (Hepatic) Clearance; 7.1 Symbols; 7.2 Function of Metabolism (Biotransformation); 7.3 Cytochrome P450; 7.3.1 Catalytic Selectivity of CYP2D6; 7.3.2 Catalytic Selectivity of CYP2C9; 7.3.3 Catalytic Selectivity of CYP3A4; 7.4 Other Oxidative Metabolism Processes; 7.4.1 Aldehyde Oxidase; 7.4.2 Flavin-Containing Monooxygenases; 7.4.3 Monoamine Oxidases; 7.5 Oxidative Metabolism and Drug Design; 7.6 Nonspecific Esterases; 7.6.1 Function of Esterases; 7.6.2 Ester Drugs as Intravenous and Topical Agents; 7.7 Prodrugs to Aid Membrane Transfer |
| Summary |
In this new edition of a bestseller, all the contents have been brought upto-date by addressing current standards and best practices in the assessmentand prediction of ADMET properties. Although the previous chapterlayout has been retained, substantial revisions have been made, with newtopics such as pro-drugs, active metabolites and transporters covered indetail in a manner useful to the Drug Discovery scientist. The authorsdiscuss the parameters and processes important for the absorption, distributionand retention of drug compounds in the body, plus the potential> |
| Bibliography |
Includes bibliographical references and index |
| Notes |
Print version record |
| Subject |
Pharmacokinetics.
|
|
Drugs -- Metabolism.
|
|
Drugs -- Design.
|
|
Pharmaceutical Preparations -- metabolism
|
|
Drug Design
|
|
Pharmacokinetics
|
|
MEDICAL -- Pharmacology.
|
|
Drugs -- Design
|
|
Drugs -- Metabolism
|
|
Pharmacokinetics
|
| Form |
Electronic book
|
| Author |
Smith, Dennis A
|
| ISBN |
9783527645305 |
|
3527645306 |
|
