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MARÍA JOSÉ GÓMEZ-LECHÓN y MARÍA TERESA DONATO AN. R. ACAD. NAC. FARM.
FIGURE 1. Drug development process depicting the different types of ADME
studies that could be performed at the various stages. Investigational New
Drug (IND). New Drug Application (NDA).
KEY ISSUES TO BE ADDRESSED AT EARLY STAGES OF
DRUG DEVELOPMENT
After intake, drugs are absorbed and distributed among the
tissues and body fluids and then eliminated or cleared, mainly by the
liver and kidneys. Therefore, the development of a new drug requires
an exhaustive characterization of not only its pharmacological
activity, but also knowledge of major enzymes involved in the
metabolite formation, and the potential enzyme-inhibiting or
enzyme-inducing properties of the drug. Therefore, over the last
decade, in vitro-based strategies in lead optimization screening
combined with ADMET screening studies have consequently been
incorporated earlier in the drug discovery phase (10).
Several metabolic key issues should be addressed at very early
stages of drug development for a better selection of the safest and
most effective drug candidates (Figure 2):
a) Drug metabolic stability and metabolic profile.
b) Metabolite identification and structure clarification.
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