PMID- 26636422
OWN - NLM
STAT- MEDLINE
DCOM- 20160314
LR  - 20160127
IS  - 0946-1965 (Print)
IS  - 0946-1965 (Linking)
VI  - 54
IP  - 2
DP  - 2016 Feb
TI  - Pharmacokinetics and tolerability of febuxostat after oral administration in 
      healthy Chinese volunteers: a randomized, open-label, singleand multiple-dose 
      three-way crossover study.
PG  - 115-24
LID - 10.5414/CP202394 [doi]
AB  - OBJECTIVE: Febuxostat is a novel non-purine selective inhibitor of xanthine 
      oxidase indicated for the chronic management of hyperuricemia in patients with 
      gout. The aim of the present study was to evaluate the pharmacokinetic properties 
      and tolerability of single and multiple oral administrations of febuxostat 
      capsules in healthy Chinese volunteers. METHODS: This openlabel, single- and 
      multiple-dose three-way crossover study was conducted in healthy Chinese 
      volunteers. Subjects were randomized to receive a single dose of febuxostat 40, 
      80, or 120 mg in separate trial periods, with a 1-week washout between periods. 
      Those allocated to the 40 mg and 80 mg dose continued into the multiple-dose 
      phase, in which they received 40 mg or 80 mg once daily for 6 consecutive days. 
      During the course of the study, blood samples were collected and the 
      concentrations of febuxostat were determined using LC-MS/MS. Pharmacokinetic 
      parameters were estimated using a noncompartmental model. Tolerability was 
      determined using clinical evaluation and monitoring of adverse events (AEs). 
      RESULTS: 12 healthy Chinese volunteers were enrolled and completed 3 treatment 
      periods. After oral administration of single doses of 40, 80, and 120 mg of 
      febuxostat, the mean (SD) Cmax was 2,835.43 (1,136.41), 5,356.75 (1,711.33), and 
      7,718.21 (2,446.34) ng/mL, respectively; the AUC0-48h was 8,821.10 (3,018.35), 
      17,854.46 (5,113.28), and 30,832.05 (10,992.20) ngxh/ mL; the AUC0-infinity was 8,990.33 
      (3,046.14), 18,193.58 (5,160.80), and 31,466.93 (1,1074.74) ngxh/mL; the t1/2 was 
      5.95 (2.71), 9.41 (7.47), and 12.34 (10.34) hours; the Cl/F was 4.81 (1.18), 4.70 
      (1.21), and 4.18(1.19) L/h; and the Vz/F was 39.66 (16.69), 62.72 (51.41), and 
      73.41 (64.84) L. After administration of multiple doses of 40 and 80 mg 
      febuxostat, the mean (SD) Cmax,ss was 2,762.38 (1,331.96) and 5,047.27 (1,456.57) 
      ng/mL; the Cmin,ss was 124.10 (6.32) and 46.93 (15.86) ng/mL; the AUCss,0-tau was 
      8,525.49 (2,160.64) and 16,757.12 (4,223.17) ngxh /mL; the steadystate plasma 
      concentration (Css) was 355.23 (90.03) and 698.21 (175.97) ng/mL; the t1/2 was 
      7.68 (3.30) and 11.33 (6.94) hours; the Cl/F was 4.99 (1.30) and 5.05 (1.22) L/h; 
      and the Vz/F was 54.10 (24.10) and 85.51 (65.99) L. No serious AEs were reported, 
      and there were no discontinuations due to AEs. CONCLUSION: The PK of febuxostat 
      exhibited dose proportional kinetics from 40 to 120 mg dose. After multiple 
      doses, the pharmacokinetic parameters of febuxostat were consistent with those 
      after single doses. There was no accumulation in febuxostat exposure in healthy 
      Chinese between multiple doses and single dose. At the doses studied, febuxostat 
      appeared to be well tolerated in these healthy volunteers.
FAU - Zhou, Huili
AU  - Zhou H
FAU - Zheng, Yunliang
AU  - Zheng Y
FAU - Wu, Guolan
AU  - Wu G
FAU - Hu, Xingjiang
AU  - Hu X
FAU - Zhai, You
AU  - Zhai Y
FAU - Iv, Duo
AU  - Iv D
FAU - Liu, Jian
AU  - Liu J
FAU - Wu, Lihua
AU  - Wu L
FAU - Shentu, Jianzhong
AU  - Shentu J
LA  - eng
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Int J Clin Pharmacol Ther
JT  - International journal of clinical pharmacology and therapeutics
JID - 9423309
RN  - 101V0R1N2E (Febuxostat)
SB  - IM
MH  - Administration, Oral
MH  - Adolescent
MH  - Adult
MH  - Cross-Over Studies
MH  - Febuxostat/administration & dosage/adverse effects/*pharmacokinetics
MH  - Female
MH  - Humans
MH  - Male
EDAT- 2015/12/05 06:00
MHDA- 2016/03/15 06:00
CRDT- 2015/12/05 06:00
PHST- 2016/01/26 00:00 [accepted]
PHST- 2015/12/05 06:00 [entrez]
PHST- 2015/12/05 06:00 [pubmed]
PHST- 2016/03/15 06:00 [medline]
AID - 13954 [pii]
AID - 10.5414/CP202394 [doi]
PST - ppublish
SO  - Int J Clin Pharmacol Ther. 2016 Feb;54(2):115-24. doi: 10.5414/CP202394.