Chapter 08 Drug Metabolism

Copyright © 2014 Elsevier Inc. All rights reserved. Figure 8.1 Effects of lipophilicity on direct renal clearance and on metabolism Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.1 Biosynthesis of penicillins Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.2 Chemical synthesis of linezolid Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.3 Cytochrome P450 oxidation of naphthalene Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.4 Addition–rearrangement mechanism for arene oxide formation Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.5 Possible fates of arene oxides Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.6 Rearrangement of arene oxides to arenols (NIH shift) Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.7 Competing pathway for NIH shift Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.8 NIH shift of chloride ion Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.9 NIH shift of nitro group Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.10 Metabolic formation and oxidation of catechols Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.11 Formation of glutathione adducts from naphthalene oxides Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.12 Deoxyribonucleic acid adduct with benzo[a]pyrene metabolite Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.13 Metabolism of carbamazepine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.14 Metabolic reactions of aflatoxin B1 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.15 C-demethylation of a flutamide metabolite Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.16 Oxidative deamination of primary amines Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.17 N-Oxidation pathways of amphetamine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.18 Amphetamine imine formation via the carbinolamine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.19 Oxidative N-dealkylation of secondary amines Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.20 Oxidative metabolism of propranolol Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.21 N-Oxidation of fenfluramine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.22 Metabolism of selegiline (deprenyl) Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.23 Oxidative metabolism of nicotine leading to C–N bond cleavage. Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.24 Metabolism of lidocaine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.25 Mechanism of cytochrome P450-catalyzed N-oxidation of tertiary aromatic amines Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.26 Possible mechanism for N-oxidation of primary arylamines Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.27 Two pathways to N-demethylation of tertiary aromatic amines Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.28 Mechanism of carbinolamine formation during oxidation of tertiary aromatic amines Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.29 Metabolic activation of primary and secondary aromatic amines Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.30 Arylhydroxamic acid N,O-acyltransferase-catalyzed activation of N-hydroxy-2-acetylaminoarenes Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.31 Initial proposals for bioactivation of acetaminophen Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.32 Bioactivation of acetaminophen via a radical intermediate Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.33 Proposed bioactivation of acetaminophen by prostaglandin H synthase Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.34 Metabolic hydroxylation of rofecoxib Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.35 Cytochrome P450-catalyzed oxidation of sulfides Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.36 S-Oxidation of tienilic acid Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.37 Oxidative dehalogenation of halothane Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.38 Reactions catalyzed by alcohol dehydrogenase Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Figure Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.39 Nitro group reduction Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.40 Reductive metabolism of nitrofurazone Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.41 Azo group reduction Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.42 Reductive metabolism of sulfasalazine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.43 Reductive dehalogenation of halothane Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.44 Competitive metabolism of R- and S-etomidate Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.45 Biosynthesis and reactions of UDP glucuronic acid Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.46 Sulfate conjugation Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.47 Bioactivation of phenacetin Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.48 Amino acid conjugation Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.49 Metabolism of brompheniramine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.50 Examples of glutathione conjugation Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.51 Metabolism of glutathione conjugates to mercapturic acid conjugates Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.52 N-Acetylation of amines Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.53 Methylation of xenobiotics Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Scheme 8.55 Metabolism of lumiracoxib to a reactive quinone-imine Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.1 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.2 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.3 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.4 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.5 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.6 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.7 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.8 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.9 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.10 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.11 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.12 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.13 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.14 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.15 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.16 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.17 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.18 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.19 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.20 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.21 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.22 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.23 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.24 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.25 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.26 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.27 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.28 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.29 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.30 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.31 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.32 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.33 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.34 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.35 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.36 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.37 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.38 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.39 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.40 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.41 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.42 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.43 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.44 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.45 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.46 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.47 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.48 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.49 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.50 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.51 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.52 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.53 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.54 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.55 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.56 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.57 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.58 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.59 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.60 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.61 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.62 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.63 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.64 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.65 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.66 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.67 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.68 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.69 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.70 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.71 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.72 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.73 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.74 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.75 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.76 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.77 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.78 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.79 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.80 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.81 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.82 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.83 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.84 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.85 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.86 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.87 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.88 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.89 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.90 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.91 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.92 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.93 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.94 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.95 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.96 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.97 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.98 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.99 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.100 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.101 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.102 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.103 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.104 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.105 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.106 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. UnnFigure 8.107 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 8.1 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 8.2 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 8.3 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 8.4 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 8.5 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 8.6 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 8.7 Copyright © 2014 Elsevier Inc. All rights reserved.

Copyright © 2014 Elsevier Inc. All rights reserved. Table 8.8 Copyright © 2014 Elsevier Inc. All rights reserved.