Pharmacokinetics and pharmacodynamics of febuxostat under fasting conditions in healthy individuals

Abstract

The aim of the present study was to investigate the pharmacokinetic and pharmacodynamic characteristics of febuxostat following the administration of single and multiple oral doses under fasting conditions to healthy individuals. Thirty-six healthy subjects were randomly divided into three groups, each containing 12 subjects (six male and six female) as follows: Group A, treated with a single oral dose of febuxostat (40 mg); group B, treated with a single oral dose of febuxostat (80 mg) followed by multiple oral doses of febuxostat for 7 days; and group C, treated with a single oral dose of febuxostat (120 mg). Blood samples were collected, and the plasma drug levels and serum uric acid (UA) concentrations were determined by clinical laboratory testing. Febuxostat displayed a linear pharmacokinetic profile for oral doses of 40 to 120 mg. Drug accumulation was not detected following multiple oral doses. When febuxostat was administered as single doses of 40, 80 and 120 mg, the 24-h UA concentration (UA24) values displayed a linear correlation with the dosage. The relationship between UA24 and the three single dose levels (40, 80 and 120 mg) was analyzed. The difference in UA24 between every single dose was significant (P<0.05). After 3 and 7 days of dosing, reductions of 46.67 and 52.69%, respectively, were observed in UA24. On day 7 of dosing, the mean reduction in the UA concentration was 51.83±7.00%. This study demonstrates that febuxostat reduces serum UA concentrations in a dose-linear manner.

Previous Dosage of Allopurinol Is a Strong Determinant of Febuxostat Efficacy

“…Similar to the previous reports, 25,26) the serum urate lowering efficacy of febuxostat was observed at an early stage, and the serum urate level was stable at 4 weeks or later (Fig. 2).…”

Side Effects and Interactions of the Xanthine Oxidase Inhibitor Febuxostat

“… Occurrence of adverse events in dependence on therapy duration (n (therapy duration up to one week) = 332; n (therapy duration over one week to one month) = 6525; n (therapy duration over one month to six months) = 3170; n (therapy duration over six months to one year) = 1297; n (therapy duration over one year) = 917; per therapy period differentiation between patients with at least one side effect (column 1), patients with at least one severe side effect (column 2), patients who dropped out of the study prematurely (column 3)) [ 2 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 ...…”

Febuxostat for Treatment of Chronic Hyperuricemia in Gout Patients

“…В отличие от аллопуринола фебуксостат практически не влияет на другие фермен-ты пуринового и пиримидинового метаболизма, что позволяет называть его селективным ингибитором ксантиноксидазы [41]. Можно полагать, что фебуксостат позволяет получить клинический эффект при значительно меньшей концен-трации препарата в плазме по сравнению с аллопурино-лом [38][39][40][41][42][43]. …”

“…У здоровых добровольцев пик плазменной концентрации наступает через 1 ч. Период полувыведения составляет 5-8 ч [41][42][43]. При повторных назначениях этот период может удлиняться [44].…”