title: Effect of Statin Treatment on Plasma 4β-Hydroxycholesterol Concentrations.
abstract: The endogenous oxysterol 4β-hydroxycholesterol may be used as a marker for the drug-metabolizing enzymes cytochrome P450 3A (CYP3A). The primary aim of this study was to investigate the effect of statin treatment on plasma 4β-hydroxycholesterol concentrations. Plasma samples from a previously performed clinical study where gallstone patients had been treated with placebo (n = 6), 20 mg fluvastatin (n = 9) or 80 mg atorvastatin (n = 9) daily for 4 weeks were analysed. Hepatic CYP3A mRNA levels had previously been shown to be unchanged in all three treatment groups. Plasma 4β-hydroxycholesterol did not change significantly (p = 0.92) in the placebo group, but treatment with low-dose fluvastatin or high-dose atorvastatin resulted in reductions in plasma concentration of 10.7% (p < 0.05) and 36.5% (p < 0.01), respectively. However, the 4β-hydroxycholesterol/cholesterol ratio did not change significantly for the patients receiving placebo or patients receiving low-dose fluvastatin. The ratio for patients receiving high-dose atorvastatin increased by 12% (p < 0.05). In conclusion, the total plasma cholesterol level is an important determinant for the plasma 4β-hydroxycholesterol level.
authors.affiliation: Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Björkhem-Bergman
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Hanna
authors.initials: H
authors.lastname: Nylén
authors.affiliation: Division of Endocrinology, Department of Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Paolo
authors.initials: P
authors.lastname: Parini
authors.affiliation: Division of Clinical Chemistry, Department of Laboratory Medicine, Karolinska Institutet, Karolinska University Hospital, Huddinge, Stockholm, Sweden.
authors.forename: Ulf
authors.initials: U
authors.lastname: Diczfalusy
mesh_terms: D000069059:Atorvastatin / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D002784:Cholesterol / Q000097:blood*; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D004347:Drug Interactions; D005229:Fatty Acids, Monounsaturated / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000077340:Fluvastatin; D042882:Gallstones / Q000188:drug therapy*; D006801:Humans; D006888:Hydroxycholesterols / Q000097:blood*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D013548:Sweden
chemical_list: D015415:Biomarkers; D005229:Fatty Acids, Monounsaturated; D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007211:Indoles; C099828:cholest-5-ene-3,4-diol; D000077340:Fluvastatin; D002784:Cholesterol; D000069059:Atorvastatin; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A