Distribution and Pharmacokinetics Models - Pesticide Biotransformation and Disposition - page 116

6

CHAPTER

Distribution and Pharmacokinetics
Models *

Ronald E. Baynes, Kelly J. Dix and Jim E. Riviere
North Carolina State University, Raleigh, NC, USA

OUTLINE
Introduction

117

Distribution 118

Total Body Water 119

Rate and Extent of Distribution 119

Volume of Distribution 120

Blood-Brain Barrier 122

Placental Transfer 122

Storage and Redistribution 123

Plasma Proteins 123

Fat 123

Other Tissues and Tissue Components 123

Storage with Repeated Exposures 124

Pharmacokinetics 124

Noncompartmental Models 125

Overview of Classical Compartmental Models 127

One-Compartment Model 127

Intravenous Bolus Dose 129

Extravascular Dose 131

Storage with Repeated Exposures 133

Multicompartment Models 136

Intravenous Bolus Dose 137

Extravascular Dose 138

Physiologically Based Models 139

Conclusions 145

References 145

INTRODUCTION
For a pesticide to elicit toxicity, it must be transferred from the external site of expo-
sure to the target site (e.g., organ, nucleic acid, receptor) and achieve a sufficiently high

* This chapter was editorially abbreviated and reformatted from K.J. Dix, 2001, Absorption, distribution and pharmaco-
kinetics, Chapter 24 in Handbook of Pesticide Toxicology (R. Krieger, Ed.), 2nd edition, Academic Press, San Diego.