title: Lipid-lowering effect of fluvastatin in relation to cytochrome P450 2C9 variant alleles frequently distributed in the Czech population.
abstract: 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.
  
  
  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.
authors: Department of Pharmacology, 1st Faculty of Medicine, Charles University and General Teaching Hospital, Prague, Czech Republic.
authors: Helena
authors: H
authors: Buzková
authors: Kristina
authors: K
authors: Pechandová
authors: Vilém
authors: V
authors: Danzig
authors: Tomá
authors: T
authors: Vareka
authors: Frantisek
authors: F
authors: Perlik
authors: Ales
authors: A
authors: Zak
authors: Ondrej
authors: O
authors: Slanar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000924:Anticholesteremic Agents / Q000009:adverse effects / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics*; D016022:Case-Control Studies; D002784:Cholesterol / Q000097:blood; D065729:Cytochrome P-450 CYP2C9; D003604:Czechoslovakia; D003710:Demography; D005229:Fatty Acids, Monounsaturated / Q000009:adverse effects / Q000494:pharmacology*; D005260:Female; D000077340:Fluvastatin; D005787:Gene Frequency / Q000235:genetics*; D005838:Genotype; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy / Q000235:genetics; D007211:Indoles / Q000009:adverse effects / Q000494:pharmacology*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015995:Prevalence
chemical_list: D000924:Anticholesteremic Agents; D005229:Fatty Acids, Monounsaturated; D007211:Indoles; D000077340:Fluvastatin; D002784:Cholesterol; C450260:CYP2C9 protein, human; D065729:Cytochrome P-450 CYP2C9; D001189:Aryl Hydrocarbon Hydroxylases