safescimet course 3.1 - Biochemical and Molecular Toxicology: Biotransformation, Bioactivation and Adverse Drug Reactions

Adverse drug reactions (ADRs), which usually occur in small subgroups of patients, are still difficult to predict in preclinical studies. Therefore knowledge of the underlying mechanisms of drug toxicity is considered crucial to improve extrapolation of animal model data to human. ADRs originate from molecular interactions of drugs or drug metabolites to critical targets in sensitive tissues. The course looks closely at biochemical and molecular aspects of toxicology especially concentrating on bioactivation processes, drug interactions and resulting ADRs. Polymorphism in genetic factors and idiosyncratic drug toxicity are also given some attention. Special emphasis is given to the biological effects of metabolites (cellular targets and defence systems) and potential safety concerns. Partipants will receive an understanding how pharmocokinetic effects (bioactivation, biotransforma- tion) impact drug safety, interrogate experimental approaches and review case studies.

Key questions addressed by the course

• Role of drug metabolism in pharmacokinetics, toxicology, and clinical adverse drug reactions
• Biotransformation of drugs to active, reactive and disproportionate metabolites
• Drug interactions and adverse events resulting from induction or inhibition of human enzymes or transporters
• Cellular targets and toxicological effects of reactive metabolites – constitutive and inducible defense systems
• ADME studies and how they integrate into drug development plans
• Current regulatory guidance on metabolites and drug interactions