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TOXICOKINETICS
×÷ÕßbusinessMEHDI BOROUJERDICollege of Health Sciences ¨C School of PharmacyUniversity of Massachusetts LowellLowell,
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International Standard Book Number-13: 978-1-4822-2135-0 (eBook - PDF)
Preface............................................................................................................................................xix
Chapter 1 The Influence of Routes of Administration on ADME.................................................1
1.1 Introduction........................................................................................................1
1.2 Pharmacokinetics (PK) and Pharmacodynamics (PD)......................................1
1.3 Toxicokinetics (TK) and Toxicodynamics (TD)................................................2
1.4 Concepts Basic to PK and TK............................................................................4
1.5 Routes of Exposure/Administration...................................................................4
1.5.1 First Category........................................................................................5
1.5.1.1 Gastrointestinal Site of Absorption.......................................5
1.5.1.2 Sublingual and Buccal Absorption........................................5
1.5.1.3 Pulmonary Route of Administration and Absorption...........9
1.5.1.4 Subcutaneous Absorption.................................................... 19
1.5.1.5 Intramuscular Route of Administration and Absorption.....22
1.5.1.6 Intraperitoneal Administration of Drugs.............................25
1.5.1.7 Rectal Route of Administration...........................................29
1.5.1.8 Intravaginal Route of Administration.................................. 31
1.5.2 Second Category: Parenteral Routes of Administration..................... 31
1.5.2.1 Intravenous Injections (IV Bolus and Infusion).................. 31
1.5.2.2 Intra-Arterial Injection........................................................ 32
1.6 Biomarkers....................................................................................................... 32
References................................................................................................................... 33
Chapter 2 Mechanisms of Absorption and Permeation of Xenobiotics....................................... 39
2.1 Introduction......................................................................................................39
2.2 Passive Diffusion..............................................................................................40
2.2.1 Transcellular and Paracellular Diffusion............................................40
2.2.1.1 Partition Coefficient............................................................. 42
2.2.1.2 Distribution Coefficient....................................................... 45
2.2.1.3 Diffusion Coefficient...........................................................46
2.2.1.4 Permeation and Permeability Constant...............................48
2.2.1.5 Estimation of Apparent Permeability Constant Using
Caco-2 Cell..........................................................................50
2.2.2 Carrier-Mediated Transcellular Diffusion.......................................... 51
2.3 Transcellular Diffusion Subject to P-Glycoprotein Efflux............................... 52
2.3.1 Pgp Structure and Function................................................................. 53
2.3.2 Pgp Computational Equations............................................................. 55
2.4 Active Transport............................................................................................... 58
2.5 Endocytosis and Pinocytosis............................................................................60
2.6 Solvent Drag, Osmosis, and Two-Pore Theory................................................60
2.7 Ion-Pair Absorption.......................................................................................... 62
References...................................................................................................................64¡¶Ò©´ú¶¯Á¦Ñ§ºÍ¶¾´ú¶¯Á¦Ñ§¡·2015×îÐÂÊé¼®
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