Pediatric Pharmacogenomics
Precision Medicine in Clinical Practice
Key Points
- Studies genetic variations affecting drug response
- Critical for pediatric dosing and safety
- Enables personalized medication selection
- Reduces adverse drug reactions
- Improves therapeutic outcomes
Core Concepts
Genetic Variants
- Drug Metabolism Enzymes
- Cytochrome P450 Family
- CYP2D6 variations
- CYP2C19 polymorphisms
- CYP2C9 variants
- CYP3A4/5 variations
- Phase II Enzymes
- TPMT variations
- UGT1A1 polymorphisms
- NAT2 variants
- Cytochrome P450 Family
- Drug Transporters
- ABCB1 (P-glycoprotein)
- SLCO1B1
- OCT1/2
- Drug Targets
- VKORC1
- HLA alleles
- Beta receptors
Clinical Applications
Therapeutic Areas
- Psychiatry/Neurology
- Antidepressants
- SSRIs (CYP2D6, CYP2C19)
- TCAs (CYP2D6)
- Response prediction
- Antiepileptics
- Carbamazepine (HLA-B*15:02)
- Valproic acid metabolism
- New-generation AEDs
- ADHD Medications
- Methylphenidate response
- Atomoxetine (CYP2D6)
- Antidepressants
- Oncology
- Chemotherapy Agents
- 6-MP (TPMT, NUDT15)
- 5-FU (DPYD)
- Methotrexate response
- Supportive Care
- Antiemetics
- Pain management
- Chemotherapy Agents
- Pain Management
- Opioids (CYP2D6)
- Codeine safety
- Tramadol efficacy
- Alternative selection
- NSAIDs (CYP2C9)
- Opioids (CYP2D6)
Testing Methods
Laboratory Techniques
- Genotyping Platforms
- Single-gene tests
- Multi-gene panels
- Custom arrays
- NGS approaches
- Phenotyping Methods
- Metabolic ratios
- Drug levels
- Enzyme activity
Clinical Implementation
Practice Integration
- Pre-emptive Testing
- Risk assessment
- Family history analysis
- Population considerations
- Point-of-Care Testing
- Urgent decisions
- Medication changes
- Dose adjustments
Interpretation Guidelines
Phenotype Assignment
- Metabolizer Status
- Poor metabolizer
- Intermediate metabolizer
- Normal metabolizer
- Rapid metabolizer
- Ultra-rapid metabolizer
- Clinical Decision Support
- Drug selection
- Dose modification
- Monitoring requirements
Special Pediatric Considerations
Developmental Factors
- Age-Related Changes
- Enzyme maturation
- Drug disposition
- Response patterns
- Growth Impacts
- Dose adjustments
- Monitoring frequency
- Safety considerations
Current Guidelines
Clinical Recommendations
- CPIC Guidelines
- Drug-gene pairs
- Clinical annotations
- Implementation guidance
- FDA Recommendations
- Required testing
- Recommended testing
- Label information
Future Directions
Emerging Areas
- New Technologies
- Point-of-care testing
- Real-time monitoring
- AI integration
- Clinical Applications
- Expanded drug coverage
- Novel biomarkers
- Precision dosing
Quality Assurance
- Laboratory Standards
- Method validation
- Quality controls
- Proficiency testing
- Result Reporting
- Standardized nomenclature
- Interpretative comments
- Clinical recommendations
