Effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and CYP3A activity in hypercholeresterolemic patients

Willrich, Maria Alice V.; Rodrigues, Alice Cristina; Cerda, Álvaro; Genvigir, Fabiana Dalla Vecchia; Arazi, Simone Sorkin; Dórea, Egı́dio Lima; Bernik, Márcia Martins Silveira; Bertolami, Marcelo Chiara; Faludi, André Árpád; Largura, Álvaro; Baudhuin, Linnea M.; Bryant, Sandra C.; Hirata, Mário Hiroyuki; Hirata, Rosário Dominguez Crespo

doi:10.1016/j.cca.2013.03.007

Cited by 20 publications

(14 citation statements)

References 39 publications

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“…Regarding the CYP3A4 *1B, we reported no association of this allele with lowdensity lipoprotein (LDL) cholesterol response [67], which was in agreement with a previous report in the Brazilian population using statins where efficacy and safety of the treatment were not affected by the CYP3A4*1B in patients using simvastatin [69].…”

Section: Cyp3a4supporting

confidence: 92%

“…As earlier stated in this review, we reported that haplotypes formed by CYP3A4*1B and the CYP3A5 variants, *3C and *1D, affect the gene expression of CYP3A5 mRNA in PBMC from hypercholesterolemic patients [67]. Moreover, a previous report of our research group related a lower decrease of LDL cholesterol values in non-African hypercholesterolemic individuals with the genotypes CYP3A5*3C/3C and CYP3A5*1D/1D [72].…”

Section: Cyp3a5supporting

confidence: 71%

“…This suggests that some polymorphisms could find their causative variant in the other gene region or even that the observed phenotype could be as a result of an additive effect. In our more recent work, we observed that although there was no influence of CYP3A4*1B on LDL cholesterol change in response to atorvastatin or CYP3A enzyme activity, when forming an haplotype with CYP3A5 variants CYP3A5*3C and CYP3A5*1D, an impaired CYP3A5 mRNA expression in peripheral blood mononuclear cells from hypercholesterolemic patients was observed [67]. In that work, we also observed a positive correlation of LDL cholesterol change in response to atorvastatin with CYP3A4 and CYP3A5 mRNA levels.…”

Section: Cyp3a4supporting

confidence: 55%

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Pharmacogenetics of drug metabolizing enzymes in Brazilian populations

Cerda

Hirata²,

Hirata³

2014

Drug Metabolism and Drug Interactions

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Phase I and II drug metabolizing enzymes (DMEs) play an important role in biotransformation of endogenous and exogenous compounds including drugs currently used in pharmacoterapy. Moreover, the genetic variability of DMEs causes important interindividual differences in drug and metabolite exposure, drug response, and risk of adverse drug reactions. We reviewed pharmacogenetics/pharmacogenomics (PGx) studies that evaluated the influence of polymorphisms in the CYPs genes - mainly CYP1, CYP2 and CYP3 gene families - and in the phase II genes - TPMT, NAT2, GSTs and UGTs - on therapeutic response in Brazilian cohorts. Ethnic admixture of Brazilians resulted in a population characterized by a unique genetic profile, in which ancestry informative markers change continuously among ethnic groups. Therefore, some of the PGx biomarkers have a different distribution among Brazilians and PGx data from well-defined ethnic groups are not applicable to Brazilian populations. PGx data focused on phase I and phase II DMEs from Brazilian studies are needed in order to establish the influence of the genetic diversity on therapeutic response to clinically relevant drugs in a population with a composition from a complex genetic admixture. These studies and their impact are discussed in this review.

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Section: Cyp3a4supporting

confidence: 92%

Section: Cyp3a5supporting

confidence: 71%

Section: Cyp3a4supporting

confidence: 55%

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Pharmacogenetics of drug metabolizing enzymes in Brazilian populations

Cerda

Hirata²,

Hirata³

2014

Drug Metabolism and Drug Interactions

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“…The same report indicated that lovastatin acts on the expression of CYP 2C9 exactly in reverse order that atorvastatin does. Another study which took place on human patients showed that atorvastatin administration increased remarkably CYP 3A4 and 3A5 mRNA expression in peripheral blood mononuclear cells of hypercholesterolemic patients (Willrich et al, 2013). One more explanation for different responses of various cells and tissues to atorvastatin may be related to its biotransformation profile.…”

Section: Discussionmentioning

confidence: 99%

Atorvastatin up-regulates the expression and activity of renal Cytochrome P450 3A2 in diabetic rats

et al. 2016

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“…It has shown susceptibility to inhibitors and inducers of CYP3A4 to produce increased or decreased plasma concentrations respectively 3 . The usage of herbal therapies along with prescription and Over-TheCounter (OTC) medications is increasing day by day.…”

mentioning

confidence: 99%

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2014

IJPSR

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Atorvastatin is a HMG-CoA reductase inhibitor used in the treatment of hyperlipidemia. Guggulsterone is a herbal product used in hyperlipidemia. The present work was aimed to study the pharmacokinetic and pharmacodynamic interactions of atorvastatin with guggulsterone in hyperlipidemic rats. Wistar albino rats with induced hyperlipidemia were divided into six groups (n=6). Blood samples were collected at predetermined time intervals from the groups treated with atorvastatin alone and in combination with guggulsterone for kinetic analysis and lipid profiles. Plasma samples were quantified for atorvastatin concentration by HPLC and then the concentration-time data were analyzed. C max , t 1/2 , AUC and MRT were significantly (p<0.05) decreased during kinetic study and clearance was significantly (p<0.05) increased in comparison with atorvastatin alone. Further, there was no significant difference in T max in all groups. The study revealed lower values [C max AUC, T 1/2 and MRT] of atorvastatin in guggulsterone treated groups. The combination of atorvastatin and guggulsterone in hyperlipidemic rats produced a significant change in lipid profiles when compared with hyperlipidemic control, but less than atorvastatin alone.

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Effects of atorvastatin on CYP3A4 and CYP3A5 mRNA expression in mononuclear cells and CYP3A activity in hypercholeresterolemic patients

Abstract: It is likely that cholesterolemia status changes promoted by atorvastatin play a role in regulating CYP3A4 and CYP3A5 mRNA expression in PBMCs, as well as CYP3A activity. CYP3A5*3C (AGT haplotype) also contributes for the variability of CYP3A5 mRNA levels in PBMCs.

Cited by 20 publications

References 39 publications

Pharmacogenetics of drug metabolizing enzymes in Brazilian populations

Pharmacogenetics of drug metabolizing enzymes in Brazilian populations

Atorvastatin up-regulates the expression and activity of renal Cytochrome P450 3A2 in diabetic rats

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