Biotransformations of Drugs and Chemicals
better than the rhesus monkey. The ex-
trapolation and scaling of drug metabolism
data from animals to humans, despite its
practical importance, is therefore still a
difFcult and imprecise science.
High-throughput Methods in Drug
The acceleration of lead candidate dis-
covery by combinatorial synthesis and
high-throughput screening methods, com-
bined with the realization that metabolism
and pharmacokinetics are critical deter-
minants of a candidate’s success, has
led to efforts to develop methods that
ties of greatest interest are absorption,
metabolism, and the inhibition and in-
duction of individual cytochrome P450
enzymes. The approaches being pursued
include computational methods for the
studies of metabolic sta-
bility, reporter constructs in which the
receptors responsible for
DNA and protein microarray analysis of
changes in metabolic enzyme levels, and
high-throughput mass spectrometric ap-
proaches to determining actual metabolite
Drug Bioavailability, Distribution
and Clearance Prediction.
Books and Reviews
to Drug Metabolism, 3rd edition, Nelson
Thornes, Cheltenham, UK.
Ioannides, C. (Ed.) (2002)
Enzyme Systems that
Metabolise Drugs and Other Xenobiotics
Wiley & Sons, New York.
Mulder, G.J. (Ed.) (1990)
in Drug Metabolism. An Integrated Approach
Taylor & ±rancis, London, New York.
Ortiz de Montellano, P.R. (Ed.) (1995)
P450: Structure, Mechanism, and Biochemistry
2nd edition, Plenum Press, New York.
Cytochrome P450: Structure, Mechanism, and
Press, New York, in press.
Cytochrome P450 Protocols
, Humana Press,
Testa, B. (1995)
Biochemistry of Redox Reactions;
Metabolism of Drugs and Other Xenobiotics
Academic Press, New York.
Testa, B., Mayer, J.M. (2003)
Hydrolysis in Drug
and Prodrug Metabolism
, Wiley-VCH, Zurich.
Woolf, T.±. (Ed.) (1999)
, Marcel Dekker, New York.
Armstrong, R.N. (1999) Kinetic and chemical
mechanism of epoxide hydrolase,
Borhan, B., Jones, A.D., Pinot, ±., Grant, D.±.,
Kurth, M.J., Hammock, B.D. (1995) Mecha-
nism of soluble epoxide hydrolase. ±orma-
tion of an
-hydroxy ester-enzyme interme-
diate through Asp-333,
J. Biol. Chem.
Benedetti, M.S., Tipton, K.±. (1998) Monoamine
oxidases and related amine oxidases as phase
I enzymes in the metabolism of xenobiotics,
Neural Transm. Suppl.
Bu, H.Z., Knuth, K., Magis, L., Teitelbaum, P.
(CYP) inhibition screening via cassette probe-
dosing strategy: III. Validation of a direct
injection/on-line guard cartridge extraction-