: Improvement of lipid metabolism:
In aged or cholesterol-loaded rats, dl-α-tocopheryl nicotinate decreases serum total cholesterol concentrations by increasing the turnover rate of cholesterol, which is considered to be due to enhanced catabolism/excretion of cholesterol. dl-α-Tocopheryl nicotinate also decreases lipid peroxide and triglyceride concentrations.
dl-α-Tocopheryl nicotinate decreases total serum cholesterol and triglyceride levels in humans, while it increases the serum levels of high-density lipoprotein (HDL) cholesterol in lipoprotein metabolism.
Enhancement of microcirculation:
In an experiment with unanesthetized rabbits, dl-α-tocopheryl nicotinate has been demonstrated to maintain vasomotion and increase peripheral blood flow in the ear conchae by directly acting on the blood vessel walls, not via the nervous system.
In a clinical trial, dl-α-tocopheryl nicotinate is more significantly effective in alleviating peripheral circulatory disturbances than coadministration of vitamin E and nicotinic acid.
Strengthening of blood vessels:
dl-α-Tocopheryl nicotinate mitigates capillary hyperpermeability in humans and decreases the number of purpura spots.
Inhibition of platelet aggregation:
dl-α-Tocopheryl nicotinate inhibits the aggregation induced by epinephrine, arachidonic acid, collagen and ADP in stimulated human platelets.
dl-α-Tocopheryl nicotinate is more potent than tocopherol and tocopherol acetate in inhibiting the aggregation induced by arachidonic acid and collagen in human platelet-rich plasma.
Restoration of arterial oxygen partial pressure:
dl-α-Tocopheryl nicotinate restores the decreased partial pressure of oxygen in human arterial blood.
Clinical efficacy: Hyperlipidemia: In open labeled clinical trials, it has been shown that statistically significant reduction for the patients of high total cholesterol before administrations, and shown that significant increase for the patients of low HDL-cholesterol before administrations. And statistically significant reduction in serum lipid peroxides was observed in patients with hyperlipidemia.
Peripheral circulatory disturbances: In double-blind and open labeled clinical trials, dl-α-tocopheryl nicotinate has been demonstrated to be useful in patients with peripheral circulatory disturbances such as arteriosclerosis obliterans.
Pharmacokinetics: Blood concentrations:
dl-α-Tocopheryl nicotinate was administered orally to 12 healthy adult male volunteers at a single dose of 600 mgnote
) after a meal, and plasma concentrations of dl-α-tocopheryl nicotinate (the unchanged drug) and tocopherol were determined. The plasma peak concentration (Cmax
=0.615 μg/mL) of the unchanged drug was reached 6 hr after administration,and thereafter declined rapidly with an elimination half-life of 4.3 hr. The peak plasma tocopherol concentration (except endogenous tocopherol) (Cmax
=1.62 μg/mL) was reached 10 hr after administration and declined gradually with an elimination half-life of 38.5 hr. (See figure.)Click on icon to see table/diagram/imageEffect of meal:
When dl-α-tocopheryl nicotinate was administered orally to 4 healthy adult male volunteers at a single dose of 600 mgnote
), the peak plasma concentration was 32 times higher and the AUC was 29 times larger after a meal than during fasting. The absorption of dl-α-tocopheryl nicotinate is significantly influenced by food intake.
Note: A single dose of 600 mg is unapproved.