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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 - Drug Des Devel Ther (2015)

Bottom Line: Accumulation index ranged from 2.0 to 2.2 after repeated dosing for 14 days.HX-1171 was well tolerated and minimally absorbed in healthy volunteers.The pharmacokinetic profile of HX-1171 was consistent with once-a-day dosing.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.

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.

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.

No MeSH data available.


Related in: MedlinePlus

The chemical structure of HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone).
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f1-dddt-9-1735: The chemical structure of HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone).

Mentions: HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone), which is a novel derivative of vitamin E, is a promising antioxidant with therapeutic potential for liver fibrosis (Figure 1). From an experimental study, HX-1171 showed a similar antioxidative activity to that of D,L-α-tocopherol against micelles, and it also exhibited approximately 4.8-fold higher anti-lipid-peroxidation activity than that of D,L-α-tocopherol against the peroxidation in liposomes.12 In another preclinical study, HX-1171 showed liver fibrosis reduction in CCl4-induced liver cirrhosis in Wistar rats.13 Additionally, HX-1171 improved against dimethylnitrosamine-induced liver fibrosis in Sprague Dawley rats.14


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 - Drug Des Devel Ther (2015)

The chemical structure of HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4376184&req=5

f1-dddt-9-1735: The chemical structure of HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone).
Mentions: HX-1171 (1-O-hexyl-2,3,5-trimethylhydroquinone), which is a novel derivative of vitamin E, is a promising antioxidant with therapeutic potential for liver fibrosis (Figure 1). From an experimental study, HX-1171 showed a similar antioxidative activity to that of D,L-α-tocopherol against micelles, and it also exhibited approximately 4.8-fold higher anti-lipid-peroxidation activity than that of D,L-α-tocopherol against the peroxidation in liposomes.12 In another preclinical study, HX-1171 showed liver fibrosis reduction in CCl4-induced liver cirrhosis in Wistar rats.13 Additionally, HX-1171 improved against dimethylnitrosamine-induced liver fibrosis in Sprague Dawley rats.14

Bottom Line: Accumulation index ranged from 2.0 to 2.2 after repeated dosing for 14 days.HX-1171 was well tolerated and minimally absorbed in healthy volunteers.The pharmacokinetic profile of HX-1171 was consistent with once-a-day dosing.

View Article: PubMed Central - PubMed

Affiliation: Department of Clinical Pharmacology and Therapeutics, College of Medicine, University of Ulsan, Asan Medical Center, Seoul, Republic of Korea.

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.

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.

No MeSH data available.


Related in: MedlinePlus