title: Statin regulation of CYP3A4 and CYP3A5 expression.
abstract: CYP3A4 and CYP3A5 are cytochrome P450 enzymes that are highly expressed in the liver and gut and metabolize endogenous compounds and xenobiotics. Statins are cholesterol-lowering drugs that are extensively metabolized by CYP3A4 and CYP3A5. The bioavailability of statins is affected by CYP3A4 and CYP3A5 and glucuronidases metabolism as well as uptake and efflux transporters that affect drug disposition. CYP3A4 and CYP3A5 variants have been demonstrated to influence the pharmacokinetics, efficacy and safety of statins. Inducers and inhibitors of CYP3A4 and CYP3A5 play an important role in reducing statin efficacy and increase the risk of adverse effects, respectively. Statins have been demonstrated to increase CYP3A expression in vitro, most likely because they are ligands to nuclear receptors (pregnane X receptor and constitutive androsterone receptor) that form heterodimers with retinoid X receptors and bind to responsive elements in the CYP3A4 and CYP3A5 promoter regions. This special report outlines the earlier studies on variability of response to statins owing to CYP3A variants and highlights findings on the induction of CYP3A4 and CYP3A5 expression by statins.
authors.affiliation: Department of Clinical and Toxicological Analysis, University of Sao Paulo, Avenue Prof. Lineu Prestes, 580, B17, 05508-05900 Sao Paulo, SP, Brazil. malicewi@usp.br
authors.forename: Maria Alice Vieira
authors.initials: MA
authors.lastname: Willrich
authors.forename: Mario Hiroyuki
authors.initials: MH
authors.lastname: Hirata
authors.forename: Rosario Dominguez Crespo
authors.initials: RD
authors.lastname: Hirata
mesh_terms: D051544:Cytochrome P-450 CYP3A / Q000235:genetics* / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide
chemical_list: D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C510164:CYP3A5 protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human