Is CYP2C9 polymorphic?
CYP2C9 is highly polymorphic, with a total of 61 alleles reported, all of which have either reduced or no enzymatic activity. A patient’s phenotype is calculated based on the genotype of the CYP2C9 allele, its heterozygosity or homozygosity (also referred to as diplotype).
What is CYP2C19 polymorphism?
CYP2C19 is a genetically polymorphic drug-metabolizing enzyme that, due to broad substrate specificity, metabolizes different classes of drugs including several psychotropic drugs, such as antidepressants (selective serotonin-reuptake inhibitors, tricyclic antidepressants), benzodiazepines, and antiepileptics.
What is polymorphism of drug metabolism?
One of the major causes of interindividual variation of drug effects is genetic variation of drug metabolism. Genetic polymorphisms of drug-metabolizing enzymes give rise to distinct subgroups in the population that differ in their ability to perform certain drug biotransformation reactions.
Which drug shows genetic polymorphism?
It is now known that N-acetyltransferase (NAT) is controlled by two genes (NAT1 and NAT2) of which NAT2 A and B are responsible for clinically significant metabolic polymorphisms. Many common drugs such as caffeine, isoniazid, nitrazepam and sulphonamides are acetylated.
What is CYP2C9 genotype?
CYP2C9 Genotyping Of special interest are those drugs with narrow therapeutic index, such as warfarin (Coumadin®), tolbutamide, and phenytoin (Dilantin®), where impairment in CYP2C9 metabolic activity might cause difficulties in dose adjustment as well as toxicity.
What is cytochrome P450 2c9 CYP2C9 substrates?
Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S-warfarin, and numerous NSAIDs. CYP2C9 activity in vivo is inducible by rifampicin.
What does it mean to be a rapid metabolizer of CYP2C19?
In people who are rapid metabolizers, the CYP2C19 enzyme has high activity. People who are rapid metabolizers break down some medicines quickly and may need different doses or a different medicine. About 29% of our patients are rapid metabolizers.
What impact can polymorphism have on drug metabolism?
Genetic polymorphisms have been identified for many drug-metabolizing enzymes, including the cytochrome P450 (CYP450) enzymes. This gives rise to distinct population phenotypes of persons who have metabolism capabilities ranging from extremely poor to extremely fast.
Why is genetic polymorphism important in drug dosing?
Genetic polymorphisms in drug transporters such as P-gp may predict the partitioning characteristics of a drug between cells and plasma. This may aid either in determining the therapeutic range or avoiding specific drugs with a particularly high risk of efficacy failure or toxicity.
Which drugs are metabolised by CYP2C9?
Accumulating evidence indicates that CYP2C9 ranks amongst the most important drug metabolizing enzymes in humans. Substrates for CYP2C9 include fluoxetine, losartan, phenytoin, tolbutamide, torsemide, S-warfarin, and numerous NSAIDs.
What induces CYP2C9?
Induction of human CYP2C9 by rifampicin, hyperforin, and phenobarbital is mediated by the pregnane X receptor. J Pharmacol Exp Ther.
What drugs do CYP2C19 metabolize?
CYP2C19 catalyzes the metabolism of several drugs, including proton pump inhibitors (PPIs) (e.g., omeprazole, lansoprazole, pantoprazole), antidepressants (e.g., citalopram and amitriptyline), antiplatelet drugs (e.g., clopidogrel), antifungals (e.g., voriconazole), and anticancer compounds (e.g., cyclophosphamide).