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Cytochrome enzymes metabolism Genetic variation in processes involved in the absorption, distribution, metabolism, or elimination of a drug can result.

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Presentation on theme: "Cytochrome enzymes metabolism Genetic variation in processes involved in the absorption, distribution, metabolism, or elimination of a drug can result."— Presentation transcript:

1 Cytochrome enzymes metabolism Genetic variation in processes involved in the absorption, distribution, metabolism, or elimination of a drug can result in changes in drug availability. Atomoxetine is metabolized by the Cytochrome P50 system, particularly CYP-2D6. Poor metabolizers (approximately 5-10% of the North American population) achieve 2-3 fold higher peak plasma concentrations of atomoxetine. The mean plasma half-life of the drug is 5.2 hours for extensive metabolizers and 21.6 hours for poor metabolizers Simpson & Perry (2003). Paediatric Drugs, 5(6), ).

2 Selected Substrates of CYP 2D6 Antidepressants Amitryptiline Clomipramine Imipramine SNRIs-SSRIs and comb. Atomoxetine Duloxetine Flouxetine Fluvoxamine Paroxetine Venlafaxine Antipsychotics Chlorpromazine, Haldol Risperidone Cough and allergy Chlorpheniramine Codeine Dextromethorphan Beta blockers Metoprolol Propanolol

3 CYP 2D6: Selected Inhibitors and Inducers Inhibitors Bupropion Cimitidine Clomipramine Escitalopram Fluoxetine Paroxetine Sertraline Inducers Dexamethasone Rifampin

4 Summary ADHD pharmacogenetics and pharmacogenomics are still in early stages There is optimism that advances in pharmacogenomics may inform treatment response and predict vulnerability to adverse events. Understanding of protein expression and function may lead to better diagnostic markers and the development of custom-made therapeutic agents Hopefully, genomics, proteomics and metabonomics in pharmacology wont just be 'fashionomics

5 Resources PharmGKB is an integrated resource about how variation in human genes leads to variation in our response to drugs Information on Cytochrome P50 system and potential drug interactions


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