title: Phase I clinical study of edaravone in healthy Chinese volunteers: safety and pharmacokinetics of single or multiple intravenous infusions.
abstract: OBJECTIVE
  The objective of this study was to investigate the safety and pharmacokinetics of edaravone administered by single or successive intravenous infusions in healthy Chinese volunteers.
  
  
  METHODS
  A total of 30 subjects (15 males and 15 females) were recruited and randomly assigned to three groups receiving edaravone doses of 20, 30, and 60 mg. All subjects received a single dose of edaravone during a 30-minute period, and only the 30 mg dose group continued to receive the same dose successively by intravenous infusion twice daily for the next 5 days. Plasma concentrations of edaravone were monitored by high-performance liquid chromatography at the following times: 15, 30, 45, 60, 75, 105, 165, 225, 300, 390, 480, 600, and 720 minutes after edaravone administration.
  
  
  RESULTS
  The area under the plasma concentration-time curve during a dosage interval (AUC(τ)) values of the single dose in the 20, 30, and 60 mg dose groups were 3.64 ± 1.37, 5.17 ± 0.93, and 11.25 ± 3.42 mg · h/L, respectively, while in the group receiving repeated dosing of 30 mg, the mean AUC(τ) value was 5.06 ± 0.89 mg · h/L. The corresponding maximum plasma drug concentration (C(max)) values were 1599.0 ± 382.6, 2378.7 ± 316.7, and 4540.1 ± 901.1 ng/mL, respectively, in the single-dose groups, and 2479.1 ± 477.9 ng/mL in the 30 mg repeated-dose group. The mean AUC(τ) and C(max) ratios between the repeated-dose group and the single-dose groups were 0.98 and 1.04. All laboratory test abnormalities (including increased alanine transaminase and triacylglycerol levels, and decreased white blood cell counts and creatinine levels) were mild and tolerable. All abnormal blood biochemical indices returned to normal levels after 7 days.
  
  
  CONCLUSIONS
  Edaravone was safe and well tolerated in the volunteers and displayed linear increases in the C(max) and AUC(τ) values.
authors: Research Division of Clinical Pharmacology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
authors: Hao
authors: H
authors: Li
authors: Kun
authors: K
authors: Xu
authors: Yongqing
authors: Y
authors: Wang
authors: Hongwen
authors: H
authors: Zhang
authors: Tianping
authors: T
authors: Li
authors: Ling
authors: L
authors: Meng
authors: Xiaojian
authors: X
authors: Gong
authors: Haibo
authors: H
authors: Zhang
authors: Ning
authors: N
authors: Ou
authors: Jinman
authors: J
authors: Ruan
mesh_terms: D000328:Adult; D000983:Antipyrine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D019540:Area Under Curve; D044466:Asian People; D002681:China; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D005260:Female; D016166:Free Radical Scavengers / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D013997:Time Factors; D055815:Young Adult
chemical_list: D016166:Free Radical Scavengers; D000077553:Edaravone; D000983:Antipyrine