Resumen de In vitro investigation of drug metabolism and toxicity in man
María José Gómez Lechón-Moliner, María Teresa Donato Martín
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 druphase. At present, the use of human in vitro hepatic models at early preclinical stages means that the process of selecting drug candidates is becoming much more rational. Several in vitro tools are available to address key issues at the earliest stages of drug development for a better candidate selection and hepatotoxicity risk assessment.
