Human Drug Metabolism provides an accessible introduction to the subject and will be particularly invaluable to those who already have some understanding of the life sciences. The new edition focuses only on essential chemical detail and includes patient case histories to illustrate the clinical consequences of changes in drug metabolism and its impact on patient welfare.

Topics covered include:

• Toxicity and drug concentration
• How metabolizing systems operate and how they impact upon drug concentration, both under drug pressure and during inhibition
• Factors affecting drug metabolism
• Age and diet are discussed
• How metabolism can lead to toxicity
• Role of drug metabolism in the commercial development of therapeutic agents as well as the pharmacology of some illicit drugs

Contents

Part 1: Introduction

• Therapeutic window
• Consequences of drug concentration changes
• Clearance
• Hepatic extraction and intrinsic clearance
• First pass and plasma drug levels
• Drug and xenobiotic metabolism

Part 2: Drug Biotransformational Systems – Origins and Aims

• Biotransforming enzymes
• Threat of lipophilic hydrocarbons
• Cell communication
• Potential food toxins
• Sites of biotransforming enzymes
• Biotransformation and xenobiotic cell entry

Part 3: How Oxidative Systems Metabolize Substrates

• Introduction
• Capture of lipophilic molecules
• Cytochrome P450s classification and basic structure
• CYPs – main and associated structures
• Human CYP families and their regulation
• Main human CYP families
• Cytochrome P450 catalytic cycle
• Flavin monooxygenases (FMOs)
• How CYP isoforms operate in vive
• Aromatic ring hydroxylation
• Alkyl oxidations
• ‘Rearrangement’ reactions
• Other oxidation processes
• Control of CYP metabolic function

Part 4: Induction of Cytochrome P450 Systems

• Introduction
• Causes of accelerated clearance
• Enzyme induction
• Mechanisms of enzyme induction
• induction – general clinical aspects

Part 5: Cytochome P450 Inhibition

• Introduction
• Inhibition of metabolism – general aspects
• Mechanisms of inhibition
• Cell transport systems and inhibition
• Major clinical consequences of inhibition of drug clearance
• Use of inhibitors for positive clinical intervention
• Summary

Part 6: Conjugation and Transport Processes

• Introduction
• Glucuronidation
• Sulphonation
• The GSH system
• Glutahione S-transferases
• Epoxide hydrolases
• Acetylation
• Methylation
• Esterases/amidases
• Amino acid conjugation (glycine or glutamate)
• Phase III transport processes
• Biotransformation-integration of processes

Part 7: Factors Affecting Drug Metabolism

• Introduction
• Genetic polymorphisms
• Effects of age on drug metabolism
• Effects of diet on drug metabolism
• Gender effects
• Smoking
• Effects of ethanol on drug metabolism
• Artificial livers
• Effects of diseases on drug metabolism
• Summary

Part 8: Role of Metabolism in Drug Toxicity

• Adverse drug reactions: definitions
• Reversible drug adverse effects: Type A
• Irreversible drug toxicity: Type B
• Type B1 necrotic reactions
• Type B2 reactions: immunotoxicity
• Type B3 reactions: role of metabolism in cancer
• Summary of biotransformational toxicity

Index

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