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.