title: Single and multiple dose pharmacokinetics and tolerability of HX-1171, a novel antioxidant, in healthy volunteers.
abstract: BACKGROUND
  HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone) is a promising antioxidant with therapeutic potential for hepatic fibrosis. The aim of this study was to investigate the tolerability and pharmacokinetics of HX-1171 in healthy volunteers.
  
  
  METHODS
  A randomized, single-blind, placebo-controlled, dose escalation study was conducted in 83 subjects. In the single ascending dose study, 20, 40, 80, 160, 300, 600, 1,200, 1,500 or 2,000 mg of HX-1171 was administered to 67 subjects. In the multiple ascending dose study, 500 or 1,000 mg was administered to 16 subjects for 14 days. The plasma and urine concentrations of HX-1171 were determined by using a validated liquid chromatography-mass spectrometry method. Pharmacokinetic parameters were obtained by non-compartmental analysis. Tolerability was assessed based on physical examinations, vital signs, clinical laboratory tests, and electrocardiograms.
  
  
  RESULTS
  Adverse events reported in the study were all mild in intensity and resolved without any sequelae. HX-1171 was rapidly and minimally absorbed with a median time at maximal concentration of 0.63-1.50 hours and slowly eliminated with a terminal half-life of 21.12-40.96 hours. Accumulation index ranged from 2.0 to 2.2 after repeated dosing for 14 days. For both the single and multiple doses administrations, urinary concentrations indicated that less than 0.01% of the HX-1171 administered was excreted in urine.
  
  
  CONCLUSIONS
  HX-1171 was well tolerated and minimally absorbed in healthy volunteers. The pharmacokinetic profile of HX-1171 was consistent with once-a-day dosing.
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Yo Han
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hee Youn
authors.initials: HY
authors.lastname: Choi
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Shi Hyang
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Hyeong-Seok
authors.initials: HS
authors.lastname: Lim
authors.affiliation: Nippon Hypox Laboratories Inc., Yamanashi, Japan.
authors.forename: Tokutaro
authors.initials: T
authors.lastname: Miki
authors.affiliation: College of Veterinary Medicine, Chungbuk National University, Cheongju, Republic of Korea.
authors.forename: Jong-Koo
authors.initials: JK
authors.lastname: Kang
authors.affiliation: Biotoxtech Co., Ltd, Cheongju, Republic of Korea.
authors.forename: Kyoung-Goo
authors.initials: KG
authors.lastname: Han
authors.affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.
authors.forename: Kyun-Seop
authors.initials: KS
authors.lastname: Bae
mesh_terms: D000328:Adult; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004361:Drug Tolerance; D064368:Healthy Volunteers; D006801:Humans; D006873:Hydroquinones / Q000008:administration & dosage* / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D008297:Male; D013058:Mass Spectrometry; D055815:Young Adult
chemical_list: D000975:Antioxidants; D006873:Hydroquinones; C081906:1-O-hexyl-2,3,5-trimethylhydroquinone
keywords: HX-1171; antioxidant; healthy subjects; pharmacokinetics; tolerability
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