Cytochrome P4502C9: an enzyme of major importance in human drug metabolism

Cytochrome P4502C9: an enzyme of major importance in human drug metabolism

1998 | John O. Miners & Donald J. Birkett
CYP2C9 is a major enzyme in human drug metabolism, involved in the metabolism of numerous drugs, including fluoxetine, losartan, phenytoin, tolbutamide, torsemide, and various NSAIDs. Its activity can be induced by rifampicin and inhibited by drugs such as amiodarone, fluconazole, and sulphonamides. Genetic polymorphisms in the CYP2C9 gene, particularly at amino acid residues 144 and 359, lead to variations in enzyme activity, with the Leu359 allele resulting in significantly reduced metabolic capacity. These variations contribute to interindividual variability in drug metabolism and dosage requirements, especially for drugs with a narrow therapeutic index. CYP2C9 is inducible by rifampicin and inhibited by various drugs, leading to clinically significant interactions. The enzyme's activity is influenced by genetic factors, environmental factors, and physiological conditions, resulting in wide interindividual variability in drug metabolism. CYP2C9 is also involved in the metabolism of non-steroidal anti-inflammatory drugs (NSAIDs), loop diuretics, and other compounds. Factors such as enzyme induction, inhibition, and genetic polymorphisms affect CYP2C9 activity, with implications for drug dosing and therapeutic outcomes. Pharmacogenetic studies have identified specific alleles associated with altered CYP2C9 activity, highlighting the importance of individualized dosing for CYP2C9 substrates. Overall, CYP2C9 plays a critical role in drug metabolism, and understanding its activity and regulation is essential for optimizing drug therapy and minimizing adverse effects.CYP2C9 is a major enzyme in human drug metabolism, involved in the metabolism of numerous drugs, including fluoxetine, losartan, phenytoin, tolbutamide, torsemide, and various NSAIDs. Its activity can be induced by rifampicin and inhibited by drugs such as amiodarone, fluconazole, and sulphonamides. Genetic polymorphisms in the CYP2C9 gene, particularly at amino acid residues 144 and 359, lead to variations in enzyme activity, with the Leu359 allele resulting in significantly reduced metabolic capacity. These variations contribute to interindividual variability in drug metabolism and dosage requirements, especially for drugs with a narrow therapeutic index. CYP2C9 is inducible by rifampicin and inhibited by various drugs, leading to clinically significant interactions. The enzyme's activity is influenced by genetic factors, environmental factors, and physiological conditions, resulting in wide interindividual variability in drug metabolism. CYP2C9 is also involved in the metabolism of non-steroidal anti-inflammatory drugs (NSAIDs), loop diuretics, and other compounds. Factors such as enzyme induction, inhibition, and genetic polymorphisms affect CYP2C9 activity, with implications for drug dosing and therapeutic outcomes. Pharmacogenetic studies have identified specific alleles associated with altered CYP2C9 activity, highlighting the importance of individualized dosing for CYP2C9 substrates. Overall, CYP2C9 plays a critical role in drug metabolism, and understanding its activity and regulation is essential for optimizing drug therapy and minimizing adverse effects.
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Understanding Cytochrome P4502C9%3A an enzyme of major importance in human drug metabolism.