Atorvastatin is a potent inhibitor of 3-hydroxy-3-methyl-glutaryl coenzyme A reductase, but its effect on bile acid synthesis is unknown. The objectives of the study were to determine the effect of atorvastatin on bile acid synthesis in patients in whom this process had not been or had been previously up-regulated by pharmacological or surgical means.Materials and methods
Four patients with heterozygous familial hypercholesterolaemia (FH) and partial ileal bypass (PIB) and 19 FH heterozygotes without PIB were treated with placebo, atorvastatin 10 mg and atorvastatin 40 mg daily, each regimen for 4 weeks. The non-PIB group was subsequently treated with bile acid (BA) sequestrant 8-16 g daily followed by co-administration of atorvastatin 10 mg, each for 4 weeks. Plasma 7α-hydroxy-4-cholesten-3-one (7α-HCO), a well-validated marker of BA synthesis was measured using high-performance liquid chromatography with UV detection.Results
The plasma 7α-HCO concentration was tenfold higher with placebo in the PIB than in the non-PIB group (418.5 ng mL−1 vs. 39.6 ng mL−1P = 0.0001). Levels decreased in PIB patients treated with atorvastatin 10 mg and 40 mg daily (350.1 ng mL−1 and 174.0 ng mL−1, P = 0.007 respectively) but did not change significantly in the non-PIB group (44.7 ng mL−1 and 28.3 ng mL− respectively). Administration of BA sequestrant to non-PIB patients increased 7α-HCO to 197.4 ng mL−1; this decreased to 106.0 ng mL−1 during co-administration of atorvastatin 10 mg daily (P = 0.0001).Conclusion
Atorvastatin decreases the rate of BA synthesis only if the latter is up-regulated by PIB or BA sequestrants, presumably by limiting the supply of newly synthesized free cholesterol.