Page - (000100) - in Biomedical Chemistry: Current Trends and Developments

AUC, area under the curve; CL, systemic clearance; Cmax, maximum concentration; DDI, drug-drug interaction; F, systemic bioavailability; LLOQ, lower limit of quantification; NCEs, new chemical entities; t1/2, half-life time; Vss, apparent volume of distribution at steady state In parallel, toxicity tests are always performed in this stage and include genotoxicity, safety pharmacology in all biological systems, reproductive toxicology in male and female animals and long-term carcinogenicity. In this context, toxicokinetics, which is defined as the generation of pharmacokinetic data under the conditions of the toxicity studies themselves, is required as an integral component of non-clinical toxicity studies (Guideline ICH S3A). The primary objective of toxicokinetics is to describe the systemic exposure achieved in animals and its relationship to the dose level and the time course of the toxicity study. These objectives are mainly achieved by measuring the plasma (or whole blood or serum) concentrations of the parent compound and/or metabolite(s) through time and determining the plasma (or whole blood or serum) AUC and Cmax. Subsequently, toxicokinetics relates the exposure achieved in toxicity studies with the toxicological