5.15 : Factors Affecting Drug Biotransformation: Biological

Biological factors significantly impact drug metabolism, influencing drug clearance, efficacy, and potential toxicity.

Species differences: Variations in enzyme systems across species can cause disparities in drug metabolism. For instance, humans may metabolize certain drugs faster than rodents, altering therapeutic effects.

Strain differences: Genetic variations within a species can result in differing enzyme activity, impacting drug response and toxicity. For example, some mouse strains may be more prone to drug-induced liver toxicity due to specific enzyme expression.

Sex differences: Hormonal disparities between sexes, such as estrogen levels, can affect enzyme activity and expression, influencing drug metabolism.

Age: Enzyme activity can alter with age, affecting drug clearance and response. Elderly individuals may exhibit reduced enzyme activity, slowing drug metabolism and increasing drug exposure. Similarly, neonates typically have reduced drug metabolism enzyme activity.

Diet: Certain foods can interact with drug-metabolizing enzymes, modifying their activity. Grapefruit juice, for instance, can inhibit certain enzymes, amplifying drug levels and potential toxicity.

Altered physiologic factors like pregnancy, hormonal imbalances, and disease states can significantly impact drug metabolism. Pregnancy can change the activity of drug-metabolizing enzymes, affecting drug clearance and efficacy. Hormonal imbalances in endocrine disorders and disease states like liver or kidney disease can also disrupt normal drug metabolism.

Temporal factors such as circadian and circannual rhythms can influence drug metabolism. Enzyme expression and activity can vary throughout the day and year, affecting drug clearance and efficacy. Some drugs may be metabolized more rapidly at specific times, leading to variations in drug response.

Comprehending all these factors is crucial for optimizing drug therapy and ensuring patient safety.