Lipid-lowering effect of fluvastatin in relation to cytochrome P450 2C9 variant alleles frequently distributed in the Czech population

被引:21
作者
Buzkova, Helena [1 ,4 ]
Pechandova, Kristina [1 ,4 ]
Danzig, Vilem [2 ,4 ]
Vareka, Tomas [3 ,4 ]
Perlik, Frantisek [1 ,4 ]
Zak, Ales [3 ,4 ]
Slanar, Ondrej [1 ,4 ]
机构
[1] Charles Univ Prague, Dept Pharmacol, Fac Med 1, Prague 12800 2, Czech Republic
[2] Charles Univ Prague, Dept Med 2, Fac Med 1, Prague 12800 2, Czech Republic
[3] Charles Univ Prague, Dept Med 4, Fac Med 1, Prague 12800 2, Czech Republic
[4] Gen Teaching Hosp, Prague, Czech Republic
来源
MEDICAL SCIENCE MONITOR | 2012年 / 18卷 / 08期
关键词
fluvastatin; CYP2C9; genetic polymorphism; SNP; hypercholesterolemia; COA REDUCTASE INHIBITORS; GENETIC POLYMORPHISMS; CLINICAL-RELEVANCE; HEALTHY-VOLUNTEERS; DRUG-INTERACTIONS; P-GLYCOPROTEIN; CYP ENZYMES; CYP2C19; PHARMACOKINETICS; TRANSPORTERS;
D O I
10.12659/MSM.883272
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
Background: CYP2C9*3 allele has been reported to correlate with increased plasma concentration of fluvastatin active form in healthy volunteers. We analyzed the correlation between the CYP2C9 genotype and cholesterol-lowering effect of fluvastatin in human hypercholesterolemic patients. Material/Methods: The study was prospective, without any interventions to standard procedures of hypolipidemic treatment. CYP2C9 genotype was determined by PCR-RFLP assay in 87 patients on concomitant fluvastatin therapy, in 48 patients on monotherapy, and in a control group of 254 healthy volunteers of Czech nationality. Biochemical and clinical data were collected before the initiation of fluvastatin treatment and 12 weeks later. Results: The frequency of CYP2C9 alleles did not differ significantly among groups of patients and volunteers. The most frequently observed allele was CYP2C9*2. Treatment with 80 mg of fluvastatin daily of 48 patients on monotherapy for 12 weeks resulted in mean low-density lipoprotein cholesterol (LDL-C) reduction by 25%, mean serum total cholesterol (TC) reduction by 21%, and mean triglyceride (TG) reduction by 28%. The CYP2C9*1/*3 genotype was associated with a decrease in LDL-C levels (by 40.0% for CYP2C9*1/*3, but only by 22.4% for CYP2C9*1/*1), and with the reduction of TC (by 28.6% in CYP2C9*1/*3 versus 20.2% in CYP2C9*1/*1). Conclusions: In hypercholesterolemic patients, LDL-C serum concentration was decreased more significantly in fluvastatin-treated subjects bearing the CYP2C9*1/*3 genotype compared to CYP2C9*1/*1 genotype. However, due to rare occurrence of some CYP genotypes, it was impossible to report a definitive positive genotype-fluvastatin effect association.
引用
收藏
页码:CR512 / CR517
页数:6
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