Factors Affecting Drug Metabolism, Including Stereochemical Aspects

Factors Affecting Drug Metabolism: It is influenced by biological, chemical, and stereochemical factors, affecting drug efficacy, clearance, and potential toxicity.

Genetic Polymorphisms
- Enzyme Variability: Differences in genes encoding drug-metabolizing enzymes (e.g., CYP450) lead to variations in metabolic rates.
- Metabolizer Phenotypes: Individuals can be poor, intermediate, extensive, or ultra-rapid metabolizers, influencing drug efficacy and toxicity.
Age and Gender
- Age: Neonates and the elderly have reduced enzyme activity, altering drug clearance.
- Gender: Hormonal differences affect enzyme expression and drug metabolism.
Disease States
- Liver & Kidney Function: Impaired liver or kidney function affects drug metabolism and excretion.
- Other Conditions: Infections and inflammation can modify enzyme activity.
Environmental Factors
- Diet & Lifestyle: Foods, herbal supplements, and habits like smoking can induce or inhibit metabolic enzymes.
- Drug–Drug Interactions: Co-administered drugs can compete for or alter enzyme activity.

Chirality and Metabolism
- Enantioselective Metabolism: Enantiomers may be metabolized at different rates due to enzyme specificity, affecting drug action and toxicity.
- Pharmacological Implications: One enantiomer may be more effective or safer than its counterpart.
Isomer-Specific Binding
- Active vs. Inactive Isomers: Only one optical isomer may contribute to therapeutic effects, while the other may be inactive or harmful.
- Regulatory Considerations: Many drugs are developed as single enantiomers to optimize efficacy and safety.
Structural Considerations in Metabolism
- Geometric Isomerism: Cis/trans isomers can have different metabolic rates due to steric hindrance.
- Conformational Flexibility: Flexible molecules interact differently with metabolic enzymes, influencing metabolism pathways.