J Clin Pharmacol. 2012 Jan;52(1):65-77. |
Use of an adaptive study design in single ascending-dose pharmacokinetics of A0001 (α-tocopherylquinone) in healthy male subjects.[Pubmed: 21343342] |
A0001 (alpha-Tocopherolquinone) is a potent antioxidant currently in development for the treatment of symptoms associated with inherited mitochondrial disorders.
METHODS AND RESULTS:
alpha-Tocopherolquinone pharmacokinetics were studied in a single-blind, adaptive design study following a single daily oral dose of placebo (n = 2) or ascending doses of alpha-Tocopherolquinone (n = 8) at 0.25 and 0.5 g under a fasted state or a 0.5- to 6-g dose with a high-fat meal. alpha-Tocopherolquinone plasma concentration-time profiles were similar across doses, reaching peak concentration within 4 to 6 hours, with concentrations returning to baseline within 24 hours. however, the nonproportionality was offset by administering alpha-Tocopherolquinone in divided doses (0.735 g, 3 times per day). The potential for an alpha-Tocopherolquinone:vitamin E interaction was also explored, as vitamin E use is prevalent in this patient population, and suggested that a clinically significant pharmacokinetic interaction is not likely. alpha-Tocopherolquinone was well tolerated with no serious adverse events or dose-limiting toxicities.
CONCLUSIONS:
These findings suggest that alpha-Tocopherolquinone has a favorable pharmacokinetic profile when administered orally with food. |
Biochem Int. 1985 May;10(5):753-61. |
Inhibition of lipid peroxidation by alpha-tocopherolquinone and alpha-tocopherolhydroquinone.[Pubmed: 4015671] |
The antioxidant effect of alpha-Tocopherolquinone and alpha-tocopherolhydroquinone was studied in liposomes and rat liver submitochondrial particles.
METHODS AND RESULTS:
Both alpha-Tocopherolquinone and alpha-tocopherolhydroquinone inhibit lipid peroxidation induced by ascorbate/Fe2+ in liposomes and by cumene hydroperoxide in submitochondrial particles. Alpha-tocopherolhydroquinone is much more effective than alpha-Tocopherolquinone in inhibiting lipid peroxidation. Submitochondrial particles, depleted of ubiquinones and reincorporated with alpha-Tocopherolquinone, are protected from lipid peroxidation only in the presence of succinate. alpha-
CONCLUSIONS:
Tocopherolquinone cannot replace endogenous ubiquinones in the respiratory chain function, nevertheless it can be reduced by the mitochondrial respiratory chain substrates, presumably through the reduced ubiquinones. |