Abstract
Both allopurinol and febuxostat, xanthine oxidase inhibitors, are effective for the treatment of patients with hyperuricemia and gout. As febuxostat exerts an efficient anti-hyperuricemic effect even by taking only once a day, there are many cases of switching from allopurinol to febuxostat. Although a comparison of the anti-hyperuricemic effects between allopurinol and febuxostat has been reported previously, there are few studies exploring the factors affecting the uric acid (UA) levels in patients after switching from allopurinol to febuxostat. To address this problem, we carried out population pharmacodynamic analysis for patients with hyperuricemia or gout whose treatment was switched from allopurinol to febuxostat. Using the non-linear mixed effect model (NONMEM), we constructed an indirect model based on 1,263 serum UA levels of 56 patients. The model described the time course of serum UA levels before and after switching from allopurinol to febuxostat. Before the initiation of treatment, the basal UA levels were increased in correlation with serum creatinine (SCr) concentrations, but no significant factors were detected in the anti-hyperuricemic effect of allopurinol. After switching to febuxostat, its anti-hyperuricemic effect was attenuated in patients concomitantly treated with loop diuretics. Although these results suggest that febuxostat can decrease the serum UA levels even in patients who have allopurinol resistance, we should pay attention to possible interactions with concomitantly administered drugs.
