Seite - (000099) - in Biomedical Chemistry: Current Trends and Developments

to determine brain concentrations and estimate the concentration ratios in relation to plasma levels (Amore, 2010). 2.1.2.2 Pharmacokinetic Evaluation on Drug Development Phases The most promising compounds found in discovery stages are then evaluated in at least two relevant animal species to obtain pharmacodynamic, pharmacokinetic, and toxicological information. The animal species are chosen according to the previous in vitro analysis. The extensive pharmacokinetic studies performed at this stage include single and multiple dose administration with several ascending doses, metabolic profiling and evaluation of drug potential to induce/inhibit drug-metabolizing enzymes. Major objectives of these studies are depicted in Table 2.1.1. Compartmental and noncompartmental methods are used to determine multiple pharmacokinetic parameters, including the maximum concentration (Cmax), time to reach the Cmax (tmax), plasma drug concentration-time curve (AUC), apparent volume of distribution at steady state (Vss), clearance (CL), elimination half-life (t1/2) and absolute or relative bioavailability, providing characterization of the pharmacokinetic profiles for a test compound. Table 2.1.3: Comparison between the strategies employed to increase the throughput of in vivo pharmacokinetic studies during drug discovery stages (Ward, 2001; Cheung, 2005; Li, 2013).