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The Influence of Genetic Variations and Drug Interactions Based on Metabolism of Antidepressants and Anticonvulsants

Author(s):

Merve Demirbugen Oz, Fezile Ozdemir and Halit Sinan Suzen*   Pages 1 - 32 ( 32 )

Abstract:


Background: The variability in drug response is highly complex and can be attributed to the polymedication, genetic polymorphisms modulating drug-metabolizing enzyme activities (cytochromes P450, CYP), physiological and environmental factors.” sentence could be revised as “The variability in drug response is highly complex and can be attributed to the polymedication, genetic polymorphisms modulating drug-metabolizing enzyme activities (cytochromeP450s (CYP)), physiological and environmental factors.

Objective: The main objective of this review is to deeply discuss the role of biotransformation in the occurrence of antidepressant and anticonvulsant induced inter individual variabilities with the focus on genetic variations and drug interactions.

Methods: An extensive search of the literature has been conducted related to biotransformation of the antidepressant and anticonvulsant agents on relationships between genetic differences and drug interactions on available databases. Following keywords are used for relevant articles: “metabolic enzyme”, “pharmacokinetic”, “antidepressant”, “anticonvulsant”, “genetic variations”, “enzyme inhibition”, “enzyme induction” and also with a list of all included antidepressant and anticonvulsants.

Results: In the present review, we provided an overview of documented clinically significant pharmacokinetic drug interactions, physiological and environmental differences. We further discuss the significance of genetic variations in drug metabolizing enzymes to underline the need for using the information on both genotype and drug interactions towards implementing better clinical outcomes through personalized medicine in neurology and psychiatry.

Conclusion: The present review clearly illustrates that interindividual differences in the biotransformation (including genetic variability of the drug metabolizing enzymes, age, sex, diet) of the antidepressant and anticonvulsant drugs, which are commonly prescribed medications globally, has a crucial role in the occurrence of adverse effects and various drug responses. Therefore, the potential results of the drug-drug interactions and individual genetic characteristics should always be considered to make pharmacotherapy safer and more effective, as they have major clinical implications.

Keywords:

Metabolism, antidepressants, anticonvulsants, adverse effect, genetic variation, enzyme inhibition, enzyme induction

Affiliation:

Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara University, Ankara,, Institute of Fo-rensic Sciences, Department of Forensic Toxicology, Ankara University, Ankara,, Faculty of Pharmacy, Department of Pharmaceutical Toxicology, Ankara University, Ankara



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