Browsing by Subject "http://www.yso.fi/onto/mesh/D010599"

The xanthine oxidase inhibitor febuxostat was recently found to inhibit the breast cancer resistance protein (BCRP) in vitro. Rosuvastatin is a substrate of BCRP and genetic variability in BCRP markedly affects rosuvastatin pharmacokinetics. The aim of this study was to investigate possible effects of febuxostat and allopurinol, another xanthine oxidase inhibitor, on rosuvastatin pharmacokinetics. In a randomized, crossover study with three phases, 10 healthy volunteers ingested once daily placebo for 7 days, 300 mg allopurinol for 7 days, or placebo for 3 days followed by 120 mg febuxostat for 4 days, and a single 10 mg dose of rosuvastatin on day 6. Febuxostat increased the peak plasma rosuvastatin concentration 2.1-fold (90% confidence interval 1.8-2.6; P=5·10-5) and the area under the plasma rosuvastatin concentration-time curve 1.9-fold (1.5-2.5; P=0.001). Allopurinol, however, had no effect on rosuvastatin pharmacokinetics. These findings suggest that febuxostat inhibits BCRP-mediated rosuvastatin efflux in the small intestine. Concomitant use of febuxostat may increase the risk of rosuvastatin-induced muscle toxicity.