Page - (000089) - in Biomedical Chemistry: Current Trends and Developments

Table 2.1.1: The role of pharmacokinetics in different stages of drug discovery and development process (Panchagnula, 2000; Chien, 2005; Bhogal, 2008; Zhang, 2012). Stages Objectives Purpose of pharmacokinetic studies Drug Discovery The global aim is to choose the optimum candidates considering their pharmacokinetic characteristics in connection with their intrinsic activity and potency and particularly: Predict in vitro ADME of NCEs; Understand the mechanisms underlying the ADME of NCEs; Screen NCEs according to their absorption; Identify the main elimination pathways and metabolic enzymes involved; Foresee the plasma protein binding of NCEs; Predict their potential to develop drug-drug interactions; Determine NCE bioavailability in rodent species. Predict pharmacokinetic parameters. In vivo fast exposure and pharmacokinetic screen of the NCEs. Pre-clinical Development The global aim is to evaluate, in laboratory animal models, the pharmacokinetics and toxicokinetics of the most promising compounds found on the drug discovery stage and: Characterize the pharmacokinetic profile of the parent compound and its main metabolites; Demonstrate biologic activity and safety in laboratory animal models; Investigate the food effect on pharmacokinetics. Select the best formulation for drug exposure and provide confidence that the predicted drug effects are achievable via the chosen route of administration; Establish safe and/or Determination of compound full exposure in animals; Determine absolute and relative bioavailability; Evaluate dose proportionality; Assess the margin of safety based on efficacy concentration and exposure data from toxicokinetic studies; Determine the best formulation for drug exposure; Predict compound pharmacokinetics in humans; Integration of pharmacokinetics and pharmacodynamics data to understand the pharmacology in animals from different species;