Development — Pharmacology In Drug Discovery And
The Vital Role of Pharmacology in Drug Discovery and Development
Phase 5: Post-Marketing (Phase IV)
Even after approval, pharmacology continues. pharmacology in drug discovery and development
Preclinical (Year 3-4)
- In vitro ADME and safety pharmacology.
- Animal efficacy models (e.g., xenografts for cancer, MCAO for stroke).
- GLP toxicology studies (28-day and 90-day).
1. Role of Pharmacology Across the Pipeline
- Target identification and validation: Establish biological relevance and druggability; use genetic models, pharmacological tools, and pathway analyses.
- Hit identification and lead optimization: Guide medicinal chemistry using structure–activity relationships (SAR), potency, selectivity, and mechanism-based assays.
- In vitro pharmacology: Characterize interaction with target(s) (binding, functional assays), off-target profiling, ADME (absorption, distribution, metabolism, excretion) screening, and cytotoxicity.
- In vivo pharmacology: Demonstrate efficacy in animal disease models, dose–response relationships, therapeutic window, and pharmacodynamic (PD) biomarkers.
- Preclinical safety pharmacology and toxicology: Assess cardiovascular, respiratory, CNS safety, genotoxicity, reproductive toxicity, and organ-specific toxicities to support IND.
- Translational pharmacology: Predict human pharmacokinetics (PK), PD, dose selection, and biomarkers for early clinical trials.
- Clinical pharmacology: Phase I–III studies to define human PK/PD, safety, dosing regimens, drug–drug interactions, special populations, and exposure–response relationships.
- Regulatory interactions: Provide pharmacology data packages (PK/PD, safety pharmacology, toxicology, bioavailability) required by regulators.
Core Battery: Testing effects on the heart, lungs, and brain. The Vital Role of Pharmacology in Drug Discovery
