Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Clinical Trial
. 2008 Mar;65(3):355-63.
doi: 10.1111/j.1365-2125.2007.03016.x. Epub 2007 Oct 22.

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

Reza Khosravan  1 , Brian Grabowski, Jing-Tao Wu, Nancy Joseph-Ridge, Laurent Vernillet
Affiliations
Clinical Trial

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

Reza Khosravan et al. Br J Clin Pharmacol. 2008 Mar.

Abstract

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.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Mean (SD) plasma concentration–time profile of febuxostat in food effect and antacid studies in healthy subjects
Figure 2
Figure 2
Predose and 24-h mean serum concentration–time profiles of uric acid following once-daily multiple oral doses of febuxostat 80 mg under fasting or nonfasting conditions in healthy subjects
See this image and copyright information in PMC

References

    1. Palella TD, Fox IH. Hyperuricemia and gout. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The Metabolic Basis of Inherited Disease. 6. New York: McGraw-Hill; 2003.
    1. Roubenoff R. Gout and hyperuricemia. Rheum Dis Clin North Am. 1990;16:539–50. - PubMed
    1. Roubenoff R, Klag MJ, Mead LA, Liang KY, Seidler AJ, Hochberg MC. Incidence and risk factors for gout in white men. JAMA. 1991;266:3004–7. - PubMed
    1. Takano Y, Hase-Aoki K, Horiuchi H, Zhao L, Kasahara Y, Kondo S, Becker MA. Selectivity of febuxostat, a novel non-purine inhibitor of xanthine oxidase/xanthine dehydrogenase. Life Sci. 2005;76:1835–47. - PubMed
    1. Becker MA, Schumacher HR, Jr, Wortmann RL, MacDonald PA, Palo WA, Eustace D, Vernillet L, Joseph-Ridge N. Febuxostat, a novel nonpurine selective inhibitor of xanthine oxidase: a twenty-eight-day, multicenter, Phase II, randomized, double-blind, placebo-controlled, dose–response clinical trial examining safety and efficacy in patients with gout. Arthritis Rheum. 2005;52:916–23. - PubMed

Publication types