Drug Des Devel Ther. 2015 Mar 23;9:1735-42. doi: 10.2147/DDDT.S79724. eCollection 2015.

Single and multiple dose pharmacokinetics and tolerability of HX-1171, a novel  antioxidant, in healthy volunteers.

Kim YH, Choi HY, Lee SH, Lim HS, Miki T, Kang JK, Han KG, Bae KS.

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 dosestudy, 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.

CONCLUSION:

HX-1171 was well tolerated and minimally absorbed in healthy volunteers. The pharmacokinetic profile of HX-1171 was consistent with once-a-day dosing.

KEYWORDS:

HX-1171; antioxidant; healthy subjects; pharmacokinetics; tolerability

PMID:

25848210

PMCID:

PMC4376184

DOI:

10.2147/DDDT.S79724