ABSTRACT

The identication of the metabolites of a novel pharmaceutical drug candidate is a fundamental part of the drug development process. It plays an important role in early drug discovery lead optimisation, such that data generated here can inuence the programme chemistry, thereby leading to drug candidates with more favourable pharmacokinetic and disposition characteristics (e.g., lower metabolic clearance) [1]. Later in drug development, the identication of drug metabolites is primarily required by the regulatory authorities in support of safety testing. It is necessary to compare the drugs’ metabolism in humans with the animals used in the toxicological evaluation, such that an appropriate assessment of the safety of any metabolites relevant to humans can be carried out. In essence, the metabolism data should be used to validate the entire safety testing programme. If adequate exposures are not demonstrated, further work is required to discharge any safety concerns regarding human metabolites. These studies form part of the overall ADME (adsorption, distribution, metabolism, excretion) package.