Clinical Drug Metabolism

Advances in the mechanistic knowledge of drug metabolism enzymology are enabling the early-stage understanding of clearance pathways that can be applied in designing clinical pharmacology programs. Clinical drug metabolism studies provide definitive characterization of the metabolic fate of drug candidates. This chapter focuses on clinical drug metabolism studies using labeled or unlabeled materials to assess disposition pathways and excretion routes of development-stage candidates. Practice for the quantification of unlabeled analytes and the structure elucidation of metabolites employs the use of liquid chromatography coupled with atmospheric pressure ionization tandem mass spectrometry. When the use of radiolabel is employed in clinical absorption, distribution, metabolism, and excretion (ADME) studies, quantitation of drug-related material in biological matrices is most commonly performed by standard iquid scintillation counting techniques. Earlier characterization of human ADME properties, perhaps even in the context of exploratory investigational new drug filings, may ultimately become routine for compounds or programs where this information forms the basis of critical success factors.