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Author:   Bernard B. Brodie ,  James R. Gillette ,  H. S. Ackermann
Publisher:   Springer-Verlag Berlin and Heidelberg GmbH & Co. KG
Imprint:   Springer-Verlag Berlin and Heidelberg GmbH & Co. K
Volume:   28 / 1
Weight:   1.070kg
ISBN:  

9783540051343

ISBN 10:   3540051341
Pages:   488
Publication Date:   01 January 1971
Audience:   Professional and scholarly ,  Professional & Vocational
Format:   Hardback
Publisher's Status:   Out of Print
Availability:   Out of stock  

Table of Contents

Section One: Routes of Drug Administration.- 1: Biological Membranes and Their Passage by Drugs.- References.- 2: Absorption of Drugs from the Gastrointestinal Tract.- I. Introduction.- II. Methods of Study.- III. Absorption from the Stomach.- IV. Intestinal Absorption of Non-Electrolytes and Weak Electrolytes.- V. Absorption of Weak Electrolytes from the Colon and Rectum.- VI. Intestinal Absorption of Organic Ions.- VII. Intestinal Absorption of Macromolecules.- VIII. Active Transport across the Intestinal Epithelium.- IX. Effect of EDTA on Drug Absorption from the Intestine.- X. Physiological Factors and Dosage Forms of Drugs as Related to Absorption from the Gastrointestinal Tract.- References.- 3: Buccal Apsorption of Drugs.- A. H. Beckett.- R. D. Hossie.- A. General Considerations.- B. Administration of Drugs via the Buccal Route.- C. Buccal Absorption Characteristics of Drugs.- I. General Method for the Buccal Absorption Test.- II. Results of the Buccal Absorption Test.- III. Absorption of Basic Drugs.- IV. Absorption of Acidic Drugs.- V. Correlation with Partition Coefficients of Acidic and Basic Drugs.- VI. Kinetics of Buccal Absorption of some Acids and Bases.- D. Distribution and Excretion of some Basic Drugs after Buccal Absorption in Man.- References.- 4: Subcutaneous and Intramuscular Injection of Drugs.- A. Introduction.- B. Anatomy of Injections.- Local Events.- C. Mechanism of Absorption.- 1. Blood Flow Measurement.- 2. Absorption Kinetics.- 3. Pellet Absorption.- 4. Dynamic Events.- 5. Molecular Weight.- D. Biological Factors.- 1. Blood Flow.- 2. Connective Tissue.- 3. Glucocorticoids.- 4. Release of Biogenic Substances.- E. Injection Solutions.- 1. Injection Volume and Concentration.- 2. Tonicity.- 3. Hydrogen Ion Concentration.- F. Delayed Uptake.- 1. Prolonged Local Effect.- 2. Prolonged Systemic Effect.- G. Complications with Injections.- 1. Microbiological Contamination.- 2. Nerve Damage.- 3. Carcinogenesis.- H. Conclusion.- References.- 5: Absorption, Distribution and Excretion of Gaseous Anesthetics.- References.- 6: Aerosols.- I. Properties of Aerosols.- II. Measurement of Aerosols.- III. Generation of Aerosols.- IV. Deposition of Aerosols in the Respiratory Tract.- V. Absorption of Aerosols - Absorptive Surfaces.- VI. Absorption Studies.- VII. Summary.- References.- 7: Absorption of Drugs through the Skin.- A. Anatomy and Physiology.- I. Evolution.- II. Some Facts and Figures.- III. Anatomy.- 1. Epidermis.- 2. The Dermis (Corium).- 3. Subcutaneous Tissue.- 4. Appendages.- 5. pH.- IV. Dermatitis.- 1. Pathology.- 2. Structure Changes.- 3. Inflammation.- 4. Patterns.- B. Pathways of Percutaneous Absorption.- I. Introduction.- II. Alternate Pathways.- III. General Conclusions.- C. Factors Affecting Percutaneous Absorption.- I. Introduction.- II. Drug-skin Interactions.- 1. Skin Hydration.- 2. Circulatory Effects.- 3. Skin Metabolism.- 4. Binding of Drugs by Skin.- III. Vehicle-Skin Interactions.- 1. Effect on Skin Hydration.- 2. Temperature Effects.- 3. Solvent Effects.- IV. Drug-Vehicle Interactions.- 1. Release from Solutions.- 2. Release from Suspensions.- 3. Other Factors Influencing Release.- V. Drug-Vehicle-Skin Interactions.- 1. Diffusion Constant.- 2. Partition Coefficient.- 3. Drug Concentration.- VI. Summary.- D. Methods for Studying Percutaneous Absorption.- I. In Vitro.- 1. Diffusion Methods without a Membrane.- 2. Diffusion Methods with Membranes.- II. In Vivo.- 1. Animal Models.- 2. Remainder Analysis.- 3. Human Skin Window.- 4. Histology.- 5. Direct Observation.- 6. Systematic Observation.- 7. Dermal Perfusion.- E. Drugs and Methods for Percutaneous Absorption Studies.- F. Treatment.- I. Dermatologic Medications.- II. Anti-Inflammatory Agents -Section One: Routes of Drug Administration.- 1: Biological Membranes and Their Passage by Drugs.- References.- 2: Absorption of Drugs from the Gastrointestinal Tract.- I. Introduction.- II. Methods of Study.- III. Absorption from the Stomach.- IV. Intestinal Absorption of Non-Electrolytes and Weak Electrolytes.- V. Absorption of Weak Electrolytes from the Colon and Rectum.- VI. Intestinal Absorption of Organic Ions.- VII. Intestinal Absorption of Macromolecules.- VIII. Active Transport across the Intestinal Epithelium.- IX. Effect of EDTA on Drug Absorption from the Intestine.- X. Physiological Factors and Dosage Forms of Drugs as Related to Absorption from the Gastrointestinal Tract.- References.- 3: Buccal Apsorption of Drugs.- A. H. Beckett.- R. D. Hossie.- A. General Considerations.- B. Administration of Drugs via the Buccal Route.- C. Buccal Absorption Characteristics of Drugs.- I. General Method for the Buccal Absorption Test.- II. Results of the Buccal Absorption Test.- III. Absorption of Basic Drugs.- IV. Absorption of Acidic Drugs.- V. Correlation with Partition Coefficients of Acidic and Basic Drugs.- VI. Kinetics of Buccal Absorption of some Acids and Bases.- D. Distribution and Excretion of some Basic Drugs after Buccal Absorption in Man.- References.- 4: Subcutaneous and Intramuscular Injection of Drugs.- A. Introduction.- B. Anatomy of Injections.- Local Events.- C. Mechanism of Absorption.- 1. Blood Flow Measurement.- 2. Absorption Kinetics.- 3. Pellet Absorption.- 4. Dynamic Events.- 5. Molecular Weight.- D. Biological Factors.- 1. Blood Flow.- 2. Connective Tissue.- 3. Glucocorticoids.- 4. Release of Biogenic Substances.- E. Injection Solutions.- 1. Injection Volume and Concentration.- 2. Tonicity.- 3. Hydrogen Ion Concentration.- F. Delayed Uptake.- 1. Prolonged Local Effect.- 2. Prolonged Systemic Effect.- G. Complications with Injections.- 1. Microbiological Contamination.- 2. Nerve Damage.- 3. Carcinogenesis.- H. Conclusion.- References.- 5: Absorption, Distribution and Excretion of Gaseous Anesthetics.- References.- 6: Aerosols.- I. Properties of Aerosols.- II. Measurement of Aerosols.- III. Generation of Aerosols.- IV. Deposition of Aerosols in the Respiratory Tract.- V. Absorption of Aerosols - Absorptive Surfaces.- VI. Absorption Studies.- VII. Summary.- References.- 7: Absorption of Drugs through the Skin.- A. Anatomy and Physiology.- I. Evolution.- II. Some Facts and Figures.- III. Anatomy.- 1. Epidermis.- 2. The Dermis (Corium).- 3. Subcutaneous Tissue.- 4. Appendages.- 5. pH.- IV. Dermatitis.- 1. Pathology.- 2. Structure Changes.- 3. Inflammation.- 4. Patterns.- B. Pathways of Percutaneous Absorption.- I. Introduction.- II. Alternate Pathways.- III. General Conclusions.- C. Factors Affecting Percutaneous Absorption.- I. Introduction.- II. Drug-skin Interactions.- 1. Skin Hydration.- 2. Circulatory Effects.- 3. Skin Metabolism.- 4. Binding of Drugs by Skin.- III. Vehicle-Skin Interactions.- 1. Effect on Skin Hydration.- 2. Temperature Effects.- 3. Solvent Effects.- IV. Drug-Vehicle Interactions.- 1. Release from Solutions.- 2. Release from Suspensions.- 3. Other Factors Influencing Release.- V. Drug-Vehicle-Skin Interactions.- 1. Diffusion Constant.- 2. Partition Coefficient.- 3. Drug Concentration.- VI. Summary.- D. Methods for Studying Percutaneous Absorption.- I. In Vitro.- 1. Diffusion Methods without a Membrane.- 2. Diffusion Methods with Membranes.- II. In Vivo.- 1. Animal Models.- 2. Remainder Analysis.- 3. Human Skin Window.- 4. Histology.- 5. Direct Observation.- 6. Systematic Observation.- 7. Dermal Perfusion.- E. Drugs and Methods for Percutaneous Absorption Studies.- F. Treatment.- I. Dermatologic Medications.- II. Anti-Inflammatory Agents - Topical Corticoids.- III. Vehicles.- References.- Section Two: Sites of Drug Transport and Disposition.- 8: The Nature of Drug-Protein Interaction.- A. Protein Structures.- B. Maintenance Forces of Protein Structure.- C. Protein Structure and Binding of Small Molecules.- I. Alterations of Structure at the Site of Binding of Small Molecules.- II. Alterations of Protein Structure at Sites Remote from the Binding Site of Small Molecules.- D. Forces in Protein-Small Molecule Interactions.- I. Bond Types.- II. Hydrophobic Bonds Absorptive Surfaces.- VI. Absorption Studies.- VII. Summary.- References.- 7: Absorption of Drugs through the Skin.- A. Anatomy and Physiology.- I. Evolution.- II. Some Facts and Figures.- III. Anatomy.- 1. Epidermis.- 2. The Dermis (Corium).- 3. Subcutaneous Tissue.- 4. Appendages.- 5. pH.- IV. Dermatitis.- 1. Pathology.- 2. Structure Changes.- 3. Inflammation.- 4. Patterns.- B. Pathways of Percutaneous Absorption.- I. Introduction.- II. Alternate Pathways.- III. General Conclusions.- C. Factors Affecting Percutaneous Absorption.- I. Introduction.- II. Drug-skin Interactions.- 1. Skin Hydration.- 2. Circulatory Effects.- 3. Skin Metabolism.- 4. Binding of Drugs by Skin.- III. Vehicle-Skin Interactions.- 1. Effect on Skin Hydration.- 2. Temperature Effects.- 3. Solvent Effects.- IV. Drug-Vehicle Interactions.- 1. Release from Solutions.- 2. Release from Suspensions.- 3. Other Factors Influencing Release.- V. Drug-Vehicle-Skin Interactions.- 1. Diffusion Constant.- 2. Partition Coefficient.- 3. Drug Concentration.- VI. Summary.- D. Methods for Studying Percutaneous Absorption.- I. In Vitro.- 1. Diffusion Methods without a Membrane.- 2. Diffusion Methods with Membranes.- II. In Vivo.- 1. Animal Models.- 2. Remainder Analysis.- 3. Human Skin Window.- 4. Histology.- 5. Direct Observation.- 6. Systematic Observation.- 7. Dermal Perfusion.- E. Drugs and Methods for Percutaneous Absorption Studies.- F. Treatment.- I. Dermatologic Medications.- II. Anti-Inflammatory Agents - Topical Corticoids.- III. Vehicles.- References.- Section Two: Sites of Drug Transport and Disposition.- 8: The Nature of Drug-Protein Interaction.- A. Protein Structures.- B. Maintenance Forces of Protein Structure.- C. Protein Structure and Binding of Small Molecules.- I. Alterations of Structure at the Site of Binding of Small Molecules.- II. Alterations of Protein Structure at Sites Remote from the Binding Site of Small Molecules.- D. Forces in Protein-Small Molecule Interactions.- I. Bond Types.- II. Hydrophobic Bonds .- III. Free Energy Considerations.- IV. Environmental Effects.- E. Albumins.- I. Structure of Albumin.- II. Albumin-Drug Interactions.- Conclusion.- References.- 9: Physical Methods for Studying Drug-Protein Binding.- A. Nonspectroscopic Techniques.- I. Rapid (or Kinetic) Dialysis.- II. Gel Filtration.- III. Heatburst Microcalorimetry.- B. Spectroscopic Techniques.- I. Ultraviolet and Visible Absorption Spectroscopy.- II. Fluorescence Spectroscopy.- III. Optical Rotatory Dispersion and Circular Dichroism.- IV. Nuclear Magnetic Resonance.- V. Other Spectroscopic Techniques.- VI. Stopped Flow and Relaxation Spectrometry.- References.- 10: Effect of Binding to Plasma Proteins on the Distribution, Activity and Elimination of Drugs.- A. Effect on Distribution and Activity.- 1. The Drug-Protein Complex.- 2. Tissue Distribution.- 3. Pharmacodynamic Activity.- 4. Antibacterial Activity.- 5. Entry into Transmembrane Compartments.- B. Effect on Elimination.- 1. Renal Excretion.- 2. Excretion into Bile.- 3. Salivary Excretion.- 4. Drug Metabolism.- C. Effect on Pharmacokinetics.- 1. A Model.- 2. Distribution.- 3. Kinetics.- D. Conclusions.- References.- 11: Competition between Drugs and Normal Substrates for Plasma and Tissue Binding Sites.- I. Introduction.- II. Bilirubin.- III. Thyroxine.- IV. Steroids.- V. Fatty Acids.- VI. Summary.- References.- 12: Drug Entry into Brain and Cerebrospinal Fluid With.- A. Introduction.- B. Anatomical Basis of Blood, Brain and CSF Barriers.- C. Blood-CSF Relationships.- D. CSF-Brain Relationships.- E. Drug Entry into CSF and Brain from Blood.- F. Methods for Studying Drug Entry and Exit.- G. Pathological Situations.- References.- 13: Translocation of Drugs into Bone.- I. Introduction.- II. The Nature of Bone.- III. Bone Mineral.- IV. Bone Mineral Dynamics and Ion Binding.- V. Binding of Heterogeneous Materials.- 1. Tetracyclines.- 2. Other Organic Drugs.- 3. Fluorides.- References.- 14: Translocation of Drugs and Other Exogenous Chemicals into Adipose Tissue.- Adipose Tissue as a Unique Body Compartment.- References.- 15: Placental Transfer of Drugs and their Distribution in Fetal Tissues.- I. Physicochemical Properties.- II. Maternal Hemodynamics and Pharmacokinetics.- 1. Maternal Hemodynamics.- 2. Maternal Pharmacokinetics.- 3. Special Considerations.- III. The Placenta.- 1. Anatomic Considerations.- 2. Hemodynamic Considerations.- 3. Other Considerations.- IV. The Fetal Circulation.- Practical Applications.- References.- 16: The Use of Autoradiography in Experimental Pharmacology.- A. Introduction.- B. Light Microscope Autoradiography.- I. Extracellular Space.- II. 3H Nicotine in Ganglia.- III. Estradiol in Uterine Tissue - Localization by Autoradiographic and Biochemical Techniques.- IV. 3H Estradiol in Nervous Tissue.- V. Neuromuscular Junction - Measurement of Active AchE Enzyme Sites in Endplates.- 1. Curare Alkaloids.- 2. Decamethonium.- 3. Diisopropylfluorophosphate (DFP).- C. Electron Microscope Autoradiography (EMAR).- I. DFP at Motor Endplates.- II. Norepinephrine at Sympathetic Nerve Terminals.- D. Organ and Whole Body Autoradiography.- References.- 17: Accumulation of Drugs at Sympathetic Nerve Endings.- A. Introduction.- B. Accumulation of Amines in Adrenergic Neurones.- C. Functional Significance of Amine Accumulation in Sympathetic Nerve Endings.- D. Effects on Norepinephrine Synthesis.- E. Chemical Sympathectomy with 6-Hydroxydopamine.- F. Uptake of Other Cyclic Bases.- Summary.- References.- Section Three: Sites of Drug Excretion.- 18: Excretion of Drugs by the Kidney.- I. The Components of the Renal Excretory System.- II. Assessment of Tubular Function.- III. Characteristics of Clearances Determined Mainly by Passive Processes.- IV. The Secretory System.- 1. Organic Anion Mechanism.- 2. The Organic Cation Mechanism.- 3. Other Components and Compounds Apparently Secreted by Two Mechanisms.- V. The Reabsorptive Systems: Bidirectional Transport.- VI. Analogous Aspects of Studies of Drug Metabolism and Excretion.- References.- 19: Excretion of Drugs in Bile.- A. Introduction.- B. Historical Aspects.- C. Types of Compounds Excreted in Bile.- D. Factors Involved in the Biliary Excretion of Chemicals.- I. Molecular Size.- II. Polarity.- 1. Polar Substances Excreted in Bile Unchanged.- 2. Compounds which are Excreted in Bile after Metabolism to a Polar Conjugate.- III. Molecular Structure and Biliary Excretion.- IV. Inter-Relationship of Molecular Size, Polarity and Structural Factors in Biliary Excretion.- E. Biliary Excretion of Quaternary Ammonium Compounds.- F. Biliary Excretion of Glycosides.- G. Mechanism of Excretion of Organic Compounds in Bile.- H. Biological Factors Influencing Biliary Excretion.- I. Binding to Plasma Proteins.- II. Metabolism.- III. Unusual Conjugates Found in Bile.- IV. Inter-Relationship of Urinary and Biliary Excretion.- V. Species Differences in Biliary Excretion.- 1. Biliary Excretion of Simple Mono- and Di-substituted Benzene Derivatives in Various Species.- 2. Biliary Excretion of Compounds of Molecular Size in the Range of 300-500 in Various Species.- 3. Biliary Excretion of Polar Compounds of Molecular Weight in the Range of 500-#8221;.- III. Free Energy Considerations.- IV. Environmental Effects.- E. Albumins.- I. Structure of Albumin.- II. Albumin-Drug Interactions.- Conclusion.- References.- 9: Physical Methods for Studying Drug-Protein Binding.- A. Nonspectroscopic Techniques.- I. Rapid (or Kinetic) Dialysis.- II. Gel Filtration.- III. Heatburst Microcalorimetry.- B. Spectroscopic Techniques.- I. Ultraviolet and Visible Absorption Spectroscopy.- II. Fluorescence Spectroscopy.- III. Optical Rotatory Dispersion and Circular Dichroism.- IV. Nuclear Magnetic Resonance.- V. Other Spectroscopic Techniques.- VI. Stopped Flow and Relaxation Spectrometry.- References.- 10: Effect of Binding to Plasma Proteins on the Distribution, Activity and Elimination of Drugs.- A. Effect on Distribution and Activity.- 1. The Drug-Protein Complex.- 2. Tissue Distribution.- 3. Pharmacodynamic Activity.- 4. Antibacterial Activity.- 5. Entry into Transmembrane Compartments.- B. Effect on Elimination.- 1. Renal Excretion.- 2. Excretion into Bile.- 3. Salivary Excretion.- 4. Drug Metabolism.- C. Effect on Pharmacokinetics.- 1. A Model.- 2. Distribution.- 3. Kinetics.- D. Conclusions.- References.- 11: Competition between Drugs and Normal Substrates for Plasma and Tissue Binding Sites.- I. Introduction.- II. Bilirubin.- III. Thyroxine.- IV. Steroids.- V. Fatty Acids.- VI. Summary.- References.- 12: Drug Entry into Brain and Cerebrospinal Fluid With.- A. Introduction.- B. Anatomical Basis of Blood, Brain and CSF Barriers.- C. Blood-CSF Relationships.- D. CSF-Brain Relationships.- E. Drug Entry into CSF and Brain from Blood.- F. Methods for Studying Drug Entry and Exit.- G. Pathological Situations.- References.- 13: Translocation of Drugs into Bone.- I. Introduction.- II. The Nature of Bone.- III. Bone Mineral.- IV. Bone Mineral Dynamics and Ion Binding.- V. Binding of Heterogeneous Materials.- 1. Tetracyclines.- 2. Other Organic Drugs.- 3. Fluorides.- References.- 14: Translocation of Drugs and Other Exogenous Chemicals into Adipose Tissue.- Adipose Tissue as a Unique Body Compartment.- References.- 15: Placental Transfer of Drugs and their Distribution in Fetal Tissues.- I. Physicochemical Properties.- II. Maternal Hemodynamics and Pharmacokinetics.- 1. Maternal Hemodynamics.- 2. Maternal Pharmacokinetics.- 3. Special Considerations.- III. The Placenta.- 1. Anatomic Considerations.- 2. Hemodynamic Considerations.- 3. Other Considerations.- IV. The Fetal Circulation.- Practical Applications.- References.- 16: The Use of Autoradiography in Experimental Pharmacology.- A. Introduction.- B. Light Microscope Autoradiography.- I. Extracellular Space.- II. 3H Nicotine in Ganglia.- III. Estradiol in Uterine Tissue - Localization by Autoradiographic and Biochemical Techniques.- IV. 3H Estradiol in Nervous Tissue.- V. Neuromuscular Junction - Measurement of Active AchE Enzyme Sites in Endplates.- 1. Curare Alkaloids.- 2. Decamethonium.- 3. Diisopropylfluorophosphate (DFP).- C. Electron Microscope Autoradiography (EMAR).- I. DFP at Motor Endplates.- II. Norepinephrine at Sympathetic Nerve Terminals.- D. Organ and Whole Body Autoradiography.- References.- 17: Accumulation of Drugs at Sympathetic Nerve Endings.- A. Introduction.- B. Accumulation of Amines in Adrenergic Neurones.- C. Functional Significance of Amine Accumulation in Sympathetic Nerve Endings.- D. Effects on Norepinephrine Synthesis.- E. Chemical Sympathectomy with 6-Hydroxydopamine.- F. Uptake of Other Cyclic Bases.- Summary.- References.- Section Three: Sites of Drug Excretion.- 18: Excretion of Drugs by the Kidney.- I. The Components of the Renal Excretory System.- II. Assessment of Tubular Function.- III. Characteristics of Clearances Determined Mainly by Passive Processes.- IV. The Secretory System.- 1. Organic Anion Mechanism.- 2. The Organic Cation Mechanism.- 3. Other Components and Compounds Apparently Secreted by Two Mechanisms.- V. The Reabsorptive Systems: Bidirectional Transport.- VI. Analogous Aspects of Studies of Drug Metabolism and Excretion.- References.- 19: Excretion of Drugs in Bile.- A. Introduction.- B. Historical Aspects.- C. Types of Compounds Excreted in Bile.- D. Factors Involved in the Biliary Excretion of Chemicals.- I. Molecular Size.- II. Polarity.- 1. Polar Substances Excreted in Bile Unchanged.- 2. Compounds which are Excreted in Bile after Metabolism to a Polar Conjugate.- III. Molecular Structure and Biliary Excretion.- IV. Inter-Relationship of Molecular Size, Polarity and Structural Factors in Biliary Excretion.- E. Biliary Excretion of Quaternary Ammonium Compounds.- F. Biliary Excretion of Glycosides.- G. Mechanism of Excretion of Organic Compounds in Bile.- H. Biological Factors Influencing Biliary Excretion.- I. Binding to Plasma Proteins.- II. Metabolism.- III. Unusual Conjugates Found in Bile.- IV. Inter-Relationship of Urinary and Biliary Excretion.- V. Species Differences in Biliary Excretion.- 1. Biliary Excretion of Simple Mono- and Di-substituted Benzene Derivatives in Various Species.- 2. Biliary Excretion of Compounds of Molecular Size in the Range of 300-500 in Various Species.- 3. Biliary Excretion of Polar Compounds of Molecular Weight in the Range of 500- Absorptive Surfaces.- VI. Absorption Studies.- VII. Summary.- References.- 7: Absorption of Drugs through the Skin.- A. Anatomy and Physiology.- I. Evolution.- II. Some Facts and Figures.- III. Anatomy.- 1. Epidermis.- 2. The Dermis (Corium).- 3. Subcutaneous Tissue.- 4. Appendages.- 5. pH.- IV. Dermatitis.- 1. Pathology.- 2. Structure Changes.- 3. Inflammation.- 4. Patterns.- B. Pathways of Percutaneous Absorption.- I. Introduction.- II. Alternate Pathways.- III. General Conclusions.- C. Factors Affecting Percutaneous Absorption.- I. Introduction.- II. Drug-skin Interactions.- 1. Skin Hydration.- 2. Circulatory Effects.- 3. Skin Metabolism.- 4. Binding of Drugs by Skin.- III. Vehicle-Skin Interactions.- 1. Effect on Skin Hydration.- 2. Temperature Effects.- 3. Solvent Effects.- IV. Drug-Vehicle Interactions.- 1. Release from Solutions.- 2. Release from Suspensions.- 3. Other Factors Influencing Release.- V. Drug-Vehicle-Skin Interactions.- 1. Diffusion Constant.- 2. Partition Coefficient.- 3. Drug Concentration.- VI. Summary.- D. Methods for Studying Percutaneous Absorption.- I. In Vitro.- 1. Diffusion Methods without a Membrane.- 2. Diffusion Methods with Membranes.- II. In Vivo.- 1. Animal Models.- 2. Remainder Analysis.- 3. Human Skin Window.- 4. Histology.- 5. Direct Observation.- 6. Systematic Observation.- 7. Dermal Perfusion.- E. Drugs and Methods for Percutaneous Absorption Studies.- F. Treatment.- I. Dermatologic Medications.- II. Anti-Inflammatory Agents - Topical Corticoids.- III. Vehicles.- References.- Section Two: Sites of Drug Transport and Disposition.- 8: The Nature of Drug-Protein Interaction.- A. Protein Structures.- B. Maintenance Forces of Protein Structure.- C. Protein Structure and Binding of Small Molecules.- I. Alterations of Structure at the Site of Binding of Small Molecules.- II. Alterations of Protein Structure at Sites Remote from the Binding Site of Small Molecules.- D. Forces in Protein-Small Molecule Interactions.- I. Bond Types.- II. Hydrophobic Bonds .- III. Free Energy Considerations.- IV. Environmental Effects.- E. Albumins.- I. Structure of Albumin.- II. Albumin-Drug Interactions.- Conclusion.- References.- 9: Physical Methods for Studying Drug-Protein Binding.- A. Nonspectroscopic Techniques.- I. Rapid (or Kinetic) Dialysis.- II. Gel Filtration.- III. Heatburst Microcalorimetry.- B. Spectroscopic Techniques.- I. Ultraviolet and Visible Absorption Spectroscopy.- II. Fluorescence Spectroscopy.- III. Optical Rotatory Dispersion and Circular Dichroism.- IV. Nuclear Magnetic Resonance.- V. Other Spectroscopic Techniques.- VI. Stopped Flow and Relaxation Spectrometry.- References.- 10: Effect of Binding to Plasma Proteins on the Distribution, Activity and Elimination of Drugs.- A. Effect on Distribution and Activity.- 1. The Drug-Protein Complex.- 2. Tissue Distribution.- 3. Pharmacodynamic Activity.- 4. Antibacterial Activity.- 5. Entry into Transmembrane Compartments.- B. Effect on Elimination.- 1. Renal Excretion.- 2. Excretion into Bile.- 3. Salivary Excretion.- 4. Drug Metabolism.- C. Effect on Pharmacokinetics.- 1. A Model.- 2. Distribution.- 3. Kinetics.- D. Conclusions.- References.- 11: Competition between Drugs and Normal Substrates for Plasma and Tissue Binding Sites.- I. Introduction.- II. Bilirubin.- III. Thyroxine.- IV. Steroids.- V. Fatty Acids.- VI. Summary.- References.- 12: Drug Entry into Brain and Cerebrospinal Fluid With.- A. Introduction.- B. Anatomical Basis of Blood, Brain and CSF Barriers.- C. Blood-CSF Relationships.- D. CSF-Brain Relationships.- E. Drug Entry into CSF and Brain from Blood.- F. Methods for Studying Drug Entry and Exit.- G. Pathological Situations.- References.- 13: Translocation of Drugs into Bone.- I. Introduction.- II. The Nature of Bone.- III. Bone Mineral.- IV. Bone Mineral Dynamics and Ion Binding.- V. Binding of Heterogeneous Materials.- 1. Tetracyclines.- 2. Other Organic Drugs.- 3. Fluorides.- References.- 14: Translocation of Drugs and Other Exogenous Chemicals into Adipose Tissue.- Adipose Tissue as a Unique Body Compartment.- References.- 15: Placental Transfer of Drugs and their Distribution in Fetal Tissues.- I. Physicochemical Properties.- II. Maternal Hemodynamics and Pharmacokinetics.- 1. Maternal Hemodynamics.- 2. Maternal Pharmacokinetics.- 3. Special Considerations.- III. The Placenta.- 1. Anatomic Considerations.- 2. Hemodynamic Considerations.- 3. Other Considerations.- IV. The Fetal Circulation.- Practical Applications.- References.- 16: The Use of Autoradiography in Experimental Pharmacology.- A. Introduction.- B. Light Microscope Autoradiography.- I. Extracellular Space.- II. 3H Nicotine in Ganglia.- III. Estradiol in Uterine Tissue - Localization by Autoradiographic and Biochemical Techniques.- IV. 3H Estradiol in Nervous Tissue.- V. Neuromuscular Junction - Measurement of Active AchE Enzyme Sites in Endplates.- 1. Curare Alkaloids.- 2. Decamethonium.- 3. Diisopropylfluorophosphate (DFP).- C. Electron Microscope Autoradiography (EMAR).- I. DFP at Motor Endplates.- II. Norepinephrine at Sympathetic Nerve Terminals.- D. Organ and Whole Body Autoradiography.- References.- 17: Accumulation of Drugs at Sympathetic Nerve Endings.- A. Introduction.- B. Accumulation of Amines in Adrenergic Neurones.- C. Functional Significance of Amine Accumulation in Sympathetic Nerve Endings.- D. Effects on Norepinephrine Synthesis.- E. Chemical Sympathectomy with 6-Hydroxydopamine.- F. Uptake of Other Cyclic Bases.- Summary.- References.- Section Three: Sites of Drug Excretion.- 18: Excretion of Drugs by the Kidney.- I. The Components of the Renal Excretory System.- II. Assessment of Tubular Function.- III. Characteristics of Clearances Determined Mainly by Passive Processes.- IV. The Secretory System.- 1. Organic Anion Mechanism.- 2. The Organic Cation Mechanism.- 3. Other Components and Compounds Apparently Secreted by Two Mechanisms.- V. The Reabsorptive Systems: Bidirectional Transport.- VI. Analogous Aspects of Studies of Drug Metabolism and Excretion.- References.- 19: Excretion of Drugs in Bile.- A. Introduction.- B. Historical Aspects.- C. Types of Compounds Excreted in Bile.- D. Factors Involved in the Biliary Excretion of Chemicals.- I. Molecular Size.- II. Polarity.- 1. Polar Substances Excreted in Bile Unchanged.- 2. Compounds which are Excreted in Bile after Metabolism to a Polar Conjugate.- III. Molecular Structure and Biliary Excretion.- IV. Inter-Relationship of Molecular Size, Polarity and Structural Factors in Biliary Excretion.- E. Biliary Excretion of Quaternary Ammonium Compounds.- F. Biliary Excretion of Glycosides.- G. Mechanism of Excretion of Organic Compounds in Bile.- H. Biological Factors Influencing Biliary Excretion.- I. Binding to Plasma Proteins.- II. Metabolism.- III. Unusual Conjugates Found in Bile.- IV. Inter-Relationship of Urinary and Biliary Excretion.- V. Species Differences in Biliary Excretion.- 1. Biliary Excretion of Simple Mono- and Di-substituted Benzene Derivatives in Various Species.- 2. Biliary Excretion of Compounds of Molecular Size in the Range of 300-500 in Various Species.- 3. Biliary Excretion of Polar Compounds of Molecular Weight in the Range of 500-1000 in Various Species.- VI. Strain and Sex Factors in Biliary Excretion.- J. Pharmacological and Toxicological Implications of Biliary Excretion of Drugs.- I. Enterohepatic Circulation.- II. Metabolism by the Gut Flora.- References.- 20: Excretion of Drugs by Milk.- I. The Mammary Gland.- II. Distribution of Drugs in the Phases of Milk.- III. Passage of Drugs from Blood Plasma to Milk.- 1. Amount of Milk.- 2. Dependence on Drug Ionization.- 3. Experimental and Theoretical Ratios M. Ultr./P. Ultr..- 4. Active Excretion.- IV. Passage of Drugs from Milk to Blood Plasma.- V. Conclusion.- References.- 21: Extracorporeal and Peritoneal Dialysis of Drugs.- A. Introduction.- B. History of the Dialysis of Poisons.- C. Membrane Aspects of Drug Dialysis.- I. Peritoneal Dialysis.- II. Hemo or Extracorporeal Dialysis.- D. Problems in Methodology.- E. The Clinical Aspects of Dialysis of Drugs.- I. Antibacterials.- II. Sedatives and Tranquilizers.- III. Analgesics.- IV. Alcohol.- V. Other Foreign Compounds and Toxicants.- VI. Fluids and Electrolytes.- F. Summary.- References.- Author Index.

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