Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects

UNLABELLED: What is already known about this subject. Febuxostat is a novel nonpurine selective inhibitor of xanthine oxidase. What this study adds. This is the first manuscript to address the effect of food and antacid on the pharmacokinetics and/or pharmacodynamics of febuxostat. The study will determine whether the drug can be administered regardless of food or antacid. It will therefore influence how the drug should be administered. AIMS: To evaluate the effects of food or antacid on the pharmacokinetics and/or pharmacodynamics of febuxostat. METHODS: Four Phase I, two-period, crossover studies were performed in healthy male and female subjects. Subjects either received single 40-mg (n = 24), multiple 80-mg (n = 24) and single 120-mg (n = 20) doses of febuxostat in fasting and nonfasting conditions, or received single 80-mg (n = 24) doses alone or with antacid. RESULTS: Food caused a decrease in C(max) (38-49%) and AUC (16-19%) of febuxostat at different dose levels following single or multiple oral dosing with febuxostat. However, a slightly greater percent decrease in serum uric acid concentrations (58% vs. 51%) after multiple dosing with 80 mg of febuxostat under nonfasting conditions was observed, which was statistically (P < 0.05) but not clinically significant. Antacid caused a decrease in C(max) (32%), but had no effect on AUC of febuxostat. Febuxostat was safe and well tolerated in all studies. CONCLUSIONS: Even though food caused a decrease in the rate and extent of absorption of febuxostat, this decrease was not associated with a clinically significant change in febuxostat pharmacodynamic effect. Despite a decrease in the absorption rate of febuxostat, antacid had no effect on the extent of febuxostat absorption. Therefore, febuxostat can be administered regardless of food or antacid intake.