Biomedical Engineering Reference
In-Depth Information
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Pharmacological
Importance of Chiral
Separations
Ann Van Eeckhaut and Yvette Michotte
CONTENTS
1.1 General Terminology of Isomerism ................................................................ 2
1.2 Chirality .......................................................................................................... 3
1.3 Stereoselectivity in Pharmacodynamics ......................................................... 5
1.4 Stereoselectivity in Pharmacokinetics ............................................................ 7
1.4.1 Absorption.......................................................................................... 8
1.4.2 Distribution ........................................................................................ 8
1.4.3 Metabolization ................................................................................... 9
1.4.3.1 Substrate Stereoselectivity ................................................. 9
1.4.3.2 Product Stereoselectivity.................................................. 10
1.4.3.3 Substrate-Product Stereoselectivity................................. 11
1.4.4 Renal Excretion................................................................................ 12
1.5 Interspecies Differences................................................................................ 12
1.6 Patient-Specii c Factors................................................................................. 12
1.6.1 Age ................................................................................................... 12
1.6.2 Gender.............................................................................................. 13
1.6.3 Genetic Factors ................................................................................ 13
1.6.4 Disease State .................................................................................... 14
1.7 Drug-Related Factors .................................................................................... 14
1.7.1 Input Rate......................................................................................... 14
1.7.2 Interactions....................................................................................... 15
1.8 Single Enantiomer versus Racemate—“Chiral Switches”............................ 15
1.9 The Need for Analytical Tools...................................................................... 17
1.10 Introduction to Capillary Electrophoresis ..................................................... 17
References ................................................................................................................ 18
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