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An. R. Acad. Nac. Farm., 2007, 73: 5-26

Revisión

In vitro investigation of drug metabolism
and toxicity in man

Recibido el 1 de febrero de 2007

MARÍA JOSÉ GÓMEZ-LECHÓN A * and
MARÍA TERESA DONATO A, B

A) Unidad de Hepatología Experimental, Centro de Investigación,
Hospital La Fe, Avda. Campanar, 21, 46009-Valencia, Spain.
B) Departamento de Bioquímica y Biología Molecular,
Facultad de Medicina, Universidad de Valencia,
Avda. Blasco Ibáñez 15, 46010-Valencia, Spain

ABSTRACT

The pharmaceutical industry is committed to marketing safer drugs with fewer
side effects, predictable pharmacokinetic properties and quantifiable drug-drug
interactions. Drug metabolism is a major determinant of drug clearance and
interindividual pharmacokinetic differences, and an indirect determinant of the
clinical efficacy and toxicity of drugs. From a commercial perspective, it is desirable
that poorly behaved compounds are removed early in the discovery phase rather
than during the more costly drug development phases. As a consequence, over the
past decade, in vitro-based strategies in lead optimization screening in conjunction
with ADMET screening studies have been incorporated earlier in the drug discovery

* Corresponding author: María José Gómez-Lechón.
Unidad de Hepatología Experimental, Centro de Investigación. Hospital Universita-
rio La Fe, Avda. Campanar, 21, E-46009-Valencia, Spain.
e-mail: gomez_mjo@gva.es; Telf.: +34 96 197 30 48; Fax: +34 96 197 30 18.
Abbreviations:
ADMET: Absorption-Distribution-Metabolism-Excretion-Toxicity.
EMEA: European Agency for the Evaluation of Medicinal products.
FDA: Food and Drug Administration.
P450: Cytochrome P450 system.

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