Optimized Dosage of Febuxostat Based on its Pharmacological Activity in Hyperuricemia Patients

• Project/Area Number: 15K18919
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Medical pharmacy
• Research Institution: Hamamatsu University School of Medicine
• Principal Investigator: Mino Yasuaki 浜松医科大学, 医学部附属病院, 薬剤師 (40586715)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: フェブキソスタット / 体内動態 / 個人間変動 / 尿酸降下薬 / 薬物動態学 / キサンチン酸化酵素 / 薬力学 / 高尿酸血症

Outline of Final Research Achievements

Xanthine oxidase Inhibitor febuxostat, is believed to its small pharmacokinetic and pharmacodynamic variability. This study aimed to evaluate pharmacokinetic and pharmacodynamic variability of febuxostat and its acyl glucuronide metabolite in clinical settings. A total of 26 patients who were receiving fixed dosage of febuxostat for at least one month were enrolled. Plasma concentration of febuxostat was determined using LC-MS/MS. Acyl glucuronide metabolite of febuxostat was unstable in human plasma and could not be determined in this study. Interindividual variation of plasma concentration of febuxostat was observed. Enzymatic activity of xanthine oxidase in plasma can be evaluated using HPLC-UV. Renal function can affect plasma concentration of febuxostat. Optimized dosage of febuxostat in hyperuricemia patients may be achieved based on plasma concentration of febuxostat and enzymatic activity of xanthine oxidase.