Chemical formula: C₃₅H₅₈O₆ Molecular mass: 574.8 g/mol
Vitamin E is the principal lipo-soluble antioxidant in the organism. It acts as a free radical chain breaking molecule, stopping the peroxidation of polyunsaturated fatty acids and it is involved in maintaining the stability and integrity of cell membranes.
The active substance d-alpha-tocopherol-polyethylene glycol 1000 succinate (tocofersolan) is a pro-drug; the active metabolite is the d-alpha-tocopherol. At low concentrations, tocofersolan forms micelles which enhance absorption of non-polar lipids such as fat-soluble vitamins. Its critical micellar concentration is low (0.04 to 0.06 mmol/l).
The hydrolysis of tocofersolan occurs in the gut lumen. Taken up by cells, the alpha-tocopherol moiety appears in chylomicrons in the lymph in a manner identical to vitamin E absorbed from the diet. Cellular uptake does not require receptors, binding proteins or metabolic processes and does not occur by pinocytosis. Absorption of deuterated tocofersolan showed a normal pattern in lipoproteins: alpha-tocopherol peaked first in chylomicrons, then in very low-density lipoproteins (VLDL) and finally in low-density lipoproteins (LDL) and high-density lipoproteins (HDL), and the disappearance portions of the curves paralleled those in control subjects.
A study in 12 healthy volunteers compared tocofersolan with a water-miscible reference vitamin E after a single oral loading dose of 1200 IU. The relative bioavailability of tocofersolan tended to be higher (Frel of 1.01 ± 1.74) with AUC0-t of 0.383 ± 0.203 µM.h/mg, Cmax of 0.013 ± 0.006, tmax of 6.0 h (6.0–24.0), and t1/2 of 29.7 h (16.0–59.5).
In a similar study tocofersolan showed a higher bioavailability than a water-miscible reference vitamin E in paediatric patients with chronic cholestasis (n=6), absorption was significantly higher on both plasma concentration maximum increase (p=0.008) and AUC (p=0.0026).
Located principally on cell membranes, within mitochondria and microsomes, vitamin E is ubiquitously distributed (red blood cells, brain, muscle, liver, platelets) and fat tissues are its major reservoir.
Vitamin E is mainly eliminated in the bile (75%) and stools, either as free tocopherol or as oxidized forms. Urine represents a minor elimination route of vitamin E (as glucuro-conjugate).
Non-clinical data in the literature reveal no special hazard for humans based on conventional studies of repeated dose toxicity, genotoxicity and toxicity to reproduction.
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