Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight
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ORIGINAL RESEARCH ARTICLE
Higher Febuxostat Exposure Observed in Asian Compared with Caucasian Subjects Independent of Bodyweight Dinko Rekić1 · Susanne Johansson1 · Jacob Leander1 Accepted: 3 September 2020 © Springer Nature Switzerland AG 2020
Abstract Background and Objective Febuxostat is a xanthine oxidase inhibitor indicated for gout and hyperuricemia. This work investigates potential clinically relevant covariates for febuxostat pharmacokinetics with a special focus on Asian race and bodyweight. Methods Febuxostat plasma concentrations from 141 male subjects were obtained from two phase II studies in patients with hyperuricemia/gout (NCT02246673, NCT02317861) and one study in healthy volunteers (NCT01883167). Subjects were administered febuxostat oral doses from 10 to 80 mg. The pharmacokinetics of febuxostat was analyzed using non-linear mixed-effects modeling as implemented in NONMEM 7.3.0. The dataset consisted of racially diverse subjects, 40% being Japanese, 10% of unknown Asian origin, 39% Caucasian, and 10% Black. Most subjects (n = 92, 63%) had normal creatinine clearance (90 mL/min), while 52 subjects (36%) had mild renal impairment (creatinine clearance > 60 to 80% relative standard error) or if they resulted in large condition numbers (e.g., > 1000), or if they were are estimated to a low value (e.g.,
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