02. Drug Distribution, Metabolism, and Elimination

Sheila A Doggrell

Discipline of Medical Sciences, Faculty of Science and Technology, Queensland University of Technology, Gardens Point, GPO Box 2434, QLD 4001, Australia

Phone +61 7 38705741 Fax +61 7 31381534 Email sheila.doggrell@qut.edu.au 

Reviewed by Elizabeth Davis, Monash University

Key words: drug distribution, protein binding, blood brain barrier, drug metabolism, Phase I, induction and inhibition of metabolism, Phase II, first pass liver metabolism, bioavailability, prodrugs, pharmacologically active metabolites, toxic metabolites, drug elimination, blood levels, elimination half-life, zero and first order kinetics, minimum effective concentrations, steady state concentrations, maintenance and loading dose

Contents

2.1 Introduction

2.2 Drug Distribution

            2.2.1 Introduction to drug distribution

            2.2.2 Protein binding

            2.2.3 Factors that modify protein binding and drug distribution?

            2.2.4 Blood brain barrier

            2.2.5 Volume of distribution

2.3 Drug Metabolism

            2.3.1 Introduction

            2.3.2 Phase I

                        2.3.2.1 Induction

                        2.3.2.2 Inhibition

            2.3.3 Phase II: Conjugation

            2.3.4 First pass metabolism and bioavailability

            2.3.5 Prodrugs

            2.3.6 Pharmacologically active metabolites

            2.3.7 Pharmacological toxic metabolites

2.4 Drug Elimination

            2.4.1 Introduction

            2.4.2 Kidney

                        2.4.2.1 Introduction

2.4.2.2 Secretion and Reabsorption

                        2.4.2.3 Renal insufficiency

            2.4.3 Other routes of excretion

2.5 Blood levels

            2.5.1 Elimination half-life

            2.5.2 First and zero order kinetics

            2.5.3 Minimum effective and steady-state concentrations

            2.5.4 Maintenance doses and loading doses