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.
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