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Effect of food or antacid on pharmacokinetics and pharmacodynamics of febuxostat in healthy subjects
Author(s) -
Khosravan Reza,
Grabowski Brian,
Wu JingTao,
JosephRidge Nancy,
Vernillet Laurent
Publication year - 2008
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2007.03016.x
Subject(s) - febuxostat , antacid , pharmacokinetics , pharmacodynamics , pharmacology , medicine , crossover study , dosing , cmax , uric acid , hyperuricemia , placebo , alternative medicine , pathology
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.