INTERPLAY OF DRUG TRANSPORTERS AND ENZYMES ON HEPATIC DRUG PROCESSING - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 709

23

INTERPLAY OF DRUG
TRANSPORTERS AND ENZYMES ON
HEPATIC DRUG PROCESSING

K. SANDY PANG, HUADONG SUN, AND SHANJUN LIU
Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Ontario, Canada

23.1. Introduction
23.2. Models of Hepatic Drug Clearance
23.3. In Vitro Systems
23.4. Simple and Zonal Physiologically Based Pharmacokinetic Models
23.5. Interplay Between Transporters and Enzymes
23.5.1. Enalapril
23.5.2. Digoxin
23.5.3. Estradiol 17 -D-Glucuronide
23.6. Conclusions
References

23.1. INTRODUCTION

The liver is a powerhouse of drug-metabolizing enzymes and is of paramount im-
portance in first-pass drug removal since the organ connects the gastrointestinal tract
to the general circulation. Removal of the orally administered dose due to first-pass
removal reduces the fraction of dose absorbed or the systemic bioavailability. 1 Upon
reaching the sinusoid, the unbound drug enters the hepatocyte by passive diffusion or