Preclinical pharmacology

• Steps towards drug discovery and development

  • Basic science and drug target identification
  • Drug target pharmacology
  • Lead drug identification
• Drug target pharmacology

  • Quantification of drug target response
  • Biomarker and assay development
• During pharmacodynamic profiling experiments are conducted in vitro or in silico initially
• Pharmacodynamic profiling allows for assay development of these molecular or cellular changes
• Following positive results in vitro, the study is moved to animal models
• The main aim of pharmacodynamic studies is to confirm the mechanism of action in vivo
• Absorption considers solubility, pH sensitivity, bioavailability, crossing BBB
• absorption is examined in vitro by analysing:

  • LogP
  • pKa
  • pH stability
• In vitro metabolism is investigated through enzyme kinetics studies (induction/inhibition)
• In vitro, distribution is explored through protein binding experiments
• There are no current in vitro methods that are as reliable as in vivo to investigate excretion