Pharmacokinetic Interactions of Concomitant Administration of Febuxostat and NSAIDs
| Autor: | Jing-Tao Wu, Laurent Vernillet, Nancy Joseph-Ridge, Reza Khosravan |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Adult
Male Naproxen Metabolic Clearance Rate Indomethacin Cmax Pharmacology Gout Suppressants Febuxostat Pharmacokinetics Reference Values Humans Medicine Drug Interactions Pharmacology (medical) Cross-Over Studies business.industry Anti-Inflammatory Agents Non-Steroidal Area under the curve Middle Aged Crossover study Confidence interval Thiazoles Area Under Curve Concomitant Female business medicine.drug |
| Zdroj: | The Journal of Clinical Pharmacology. 46:855-866 |
| ISSN: | 0091-2700 |
| DOI: | 10.1177/0091270006289848 |
| Popis: | 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 (Cmax) 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 Cmax and AUC24, 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. |
| Databáze: | OpenAIRE |
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