Clinical Significance of Cytochrome P450 3A (CYP3A) Polymorphism
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Abstract
Cytochrome P450 (CYP) plays a major role in catalyzing metabolism of lipophilic endogenous and exogenous substrates, leading to detoxification of exogenous compounds and catabolism of endogenous compounds. Polymorphism of CYP450 is a phenomenon of variation of CYP450 that causes alteration in metabolic rate and pharmacological activity. CYP3A polymorphism has been clinically reported to be associated with failure of medication from a change of pharmacokinetics. CYP3A4*1B, CYP3A4*1G, and CYP3A5*3 alleles are mostly involved in reduction of CYP3A enzymes. For example, CYP3A5*3 carriers exhibited a tendency to be suffered from high dose of atorvastatin-induced muscle damage due to lower clearance of the drug. Considering CYP3A polymorphism on drug interactions, CYP3A5*3 patients who received clopidogrel concomitantly with CYP3A4 inhibitors, e.g. itraconazole, have increased the risk of atherothrombotic event after coronary angioplasty according to higher platelet aggregation activity. Concerning CYP3A polymorphism on disease complications, heavy smokers of both sexes with CYP3A4*1B allele were significantly found an increase in a risk of lung cancer than those of CYP3A4*1A with lower smoking. The present review article brings an overview of CYP3A polymorphism and its clinical significance on 3 pharmacotherapeutic aspects, including pharmacokinetics, drug interactions, and disease complications.
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