Pharmacokinetics and Safety of Enzalutamide in Healthy Chinese Male Volunteers

Purpose: This open-label, single-dose study evaluated the pharmacokinetic profiles of enzalutamide and its major metabolites and the safety of enzalutamide in healthy, Chinese male volunteers. Methods: Fourteen volunteers (median age, 28.5 years) received a single oral dose of enzalutamide (160 mg) under fasting conditions on day 1 and were followed for 50 days. Pharmacokinetic profiles were obtained for enzalutamide and its major metabolites, carboxylic acid metabolite (M1; inactive metabolite) and N-desmethyl enzalutamide (M2; active metabolite), on day 1 up to 1176 hours (49 days). Safety data were also collected. Findings: Enzalutamide plasma concentration rapidly increased (median T-max, 1.5 hours) followed by a slow decrease (mean t(1)(/2), 90.7 hours). M1 and M2 plasma concentrations increased gradually with a median T(max )of 72.0 and 121 hours, respectively. M1 and M2 mean metabolite-to-parent ratios were 0.2 and 1.3, respectively. Mean AUC(0-infinity) of enzalutamide plus M2 was 828 mu g h/mL versus 368 mu g h/mL for enzalutamide alone. Mean tip, maximum concentration, and T-max of enzalutamide plus M2 were comparable with those of enzalutamide. Drug-related treatment-emergent adverse events were reported in 4 men (28.6%): 1 each of upper respiratory tract infection, chest discomfort, increased blood bilirubin, and decreased white blood cell count. No deaths or serious treatment-emergent adverse events were observed. (C) 2018 Published by Elsevier Inc.