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Pharmacokinetic Interactions of Concomitant Administration of Febuxostat and NSAIDs
Author(s) -
Khosravan Reza,
Wu JingTao,
JosephRidge Nancy,
Vernillet Laurent
Publication year - 2006
Publication title -
the journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.92
H-Index - 116
eISSN - 1552-4604
pISSN - 0091-2700
DOI - 10.1177/0091270006289848
Subject(s) - febuxostat , naproxen , pharmacokinetics , medicine , confidence interval , crossover study , pharmacology , concomitant , uric acid , hyperuricemia , alternative medicine , pathology , placebo
To evaluate the effect of febuxostat on the pharmacokinetics of indomethacin and naproxen and vice versa, 2 multiple‐dose, 3‐period crossover studies were performed in healthy subjects. In study 1, subjects received febuxostat 80 mg once daily, indomethacin 50 mg twice daily, or both. In study 2, subjects received febuxostat 80 mg, naproxen 500 mg twice daily, or both. Twenty‐four‐hour blood samples were collected on day 5 in study 1 and day 7 in study 2. In study 1, 90% confidence intervals of geometric mean ratios for maximum plasma concentration (C max ) and area under the curve (AUC) were within the 0.80 to 1.25 no‐effect range for febuxostat and indomethacin. In study 2, 90% confidence intervals for febuxostat C max and AUC extended above that range, with increases of 28% and 40% in C max and AUC 24 , respectively. However, 90% confidence intervals for naproxen C max and AUC were within the 0.80 to 1.25 range. Febuxostat had no effect on the plasma pharmacokinetics of indomethacin and naproxen. Similarly, indomethacin had no effect on the plasma pharmacokinetics of febuxostat. Although naproxen caused an increase in plasma exposure to febuxostat, this increase is not expected to be clinically significant. Therefore, based on the plasma pharmacokinetic data in healthy subjects, febuxostat may be administered with indomethacin or naproxen with no dose adjustments for febuxostat, indomethacin, or naproxen.