Effect of Statin Treatment on Plasma 4β‐Hydroxycholesterol Concentrations

• Published in: Basic & clinical pharmacology & toxicology Vol. 118; no. 6; pp. 499 - 502
• Main Authors: Björkhem‐Bergman, Linda, Nylén, Hanna, Eriksson, Mats, Parini, Paolo, Diczfalusy, Ulf
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.06.2016
• Subjects: Atorvastatin; Atorvastatin Calcium - pharmacology; Atorvastatin Calcium - therapeutic use; Biomarkers - blood; Calculi; Cholesterol; Cholesterol - blood; Cytochrome; Cytochrome P-450 CYP3A - metabolism; Cytochrome P450; Drug Interactions; Fatty Acids, Monounsaturated - pharmacology; Fatty Acids, Monounsaturated - therapeutic use; Female; Fluvastatin; Gallstones - drug therapy; Humans; Hydroxycholesterols - blood; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles - pharmacology; Indoles - therapeutic use; Male; Medicin och hälsovetenskap; Middle Aged; mRNA; Patients; Plasma; Statins; Sweden
• ISSN: 1742-7835; 1742-7843; 1742-7843
• DOI: 10.1111/bcpt.12537

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.