Spring Intro 2023

Mike Kelly

Basic Principles: Pharmacokinetics - Metabolism

• Regulatory requirement to identify significant metabolites i.e. those that are > 10% of circulating drug related material. • Ensure appropriate pre-clinical toxicology cover of significant metabolites in man • Cytochrome P450 (CYP450) enzymes are main enzymes involved in metabolism • Enzyme induction/inhibition may result in drug-drug interactions • Polymorphisms may result in varying enzyme activity (CYP2D6 etc)

Clinical Example of Metabolic Polymorphism: CYP2D6

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Basic Principles: Pharmacokinetics - Excretion

 Excretion ● Removal of unchanged drug and/or metabolites from the body ● Via urine , bile , feces , sweat, lungs, milk ● If renal, hepatic or biliary elimination are major routes of excretion, need to consider how age or disease states resulting in impairment of the function of these organs, impact elimination of drug

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