18

ADME STUDIES IN ANIMALS

AND HUMANS: EXPERIMENTAL

DESIGN, METABOLITE PROFILING

AND IDENTIFICATION,

AND DATA PRESENTATION

DONGLUZHANG ANDS. NILGUNCOMEZOGLU

18.1 OBJECTIVES, RATIONAL, AND REGULATORY COMPLIANCE

Absorption, distribution, metabolism, and excretion (ADME) studies in
discovery and exploratory development stages of drugs are conducted to
assess the metabolism and excretion of a radiolabeled drug following a single
administration (intravenous or oral) to rodents (rats or mice), nonrodents
(dogs or monkeys), special species such as rabbits, and humans. These studies
will (1) evaluate the exposures of the parent compound and its metabolites in
animals and humans for validation of toxicological species, (2) identify the
major metabolic pathways in humans to support drug–drug interaction studies,
and (3) establish the rate and route of excretion of a drug candidate, and in
addition, (4) provide metabolism data of drugs for regulatory filing.
Nonclinical ADME studies are used to link the animal pharmacology and
toxicology studies to humans. Data obtained from the animal metabolism and
excretory pathways of a drug may be useful to design a clinical mass balance
study. Once in the development stage, ADME data in animals and humans
with radiolabeled materials will reveal the major circulating metabolite(s) and

Drug Metabolism in Drug Design and Development, Edited by Donglu Zhang, Mingshe Zhu
and W. Griffith Humphreys
Copyright#2008 John Wiley & Sons, Inc.

573