Tocofersolan

Absorption

The bioavailability of vitamin E from tocofersolan is unique from than that of other medicinal products .
Due to its amphipathic property in which it forms its own micelles, tocofersolan is readily taken up into enterocytes, even in the absence of bile salts; fat-soluble d-alpha-tocopherol is then released after hydrolysis. This formulation enhances the absorption of d-alpha-tocopherol compared to the administration of free d-alpha-tocopherol. Additionally, tocophersolan may enhance the absorption of water-insoluble agents and other fat-soluble vitamins .
Tocofersolan is a pro-drug; the active metabolite is the d-alpha-tocopherol. At low concentrations, tocofersolan forms micelles which improve the absorption of non-polar lipids such as other fat-soluble vitamins. Its required micellar concentration is low (0.04 to 0.06 mmol/l) .
A pharmacokinetic study of 12 healthy subjects compared tocofersolan with a water-miscible reference vitamin E after one single oral loading dose of 1200 IU (international units). The relative bioavailability of tocofersolan was found to be (Frel of 1.01 ± 1.74) with AUC0-t of 0.383 ± 0.203μM.h/mg, Cmax of 0.013 ± 0.006, Tmax of 6.0 h (6.0 – 24.0) .
For more information about Vitamin E metabolism, please visit the drug entry Tocopherol.

Toxicity

> 7 g/kg ( Rat )
Common adverse reactions
The most commonly reported adverse reaction during treatment is diarrhea . High doses of Vitamin E may cause diarrhea, abdominal pain, and other gastrointestinal conditions. In the case of an overdose, symptomatic treatment should be provided . High doses of vitamin E have been reported to increase bleeding tendency in patients with Vitamin K deficiency, or patients taking oral anti-vitamins K treatment . Therefore, careful monitoring of the prothrombin time and international normalized ratio (INR) are advised. A possible adjustment of the dose of oral anticoagulant during and after treatment with Vedrop may be necessary .
Renal impairment
Data regarding patients with renal impairment are limited, this drug should be administered with caution and those with renal impairment or dehydration should be closely followed .
Hepatic impairment
This drug should be administered with caution in patients with liver impairment and under close monitoring of the liver function tests in such patients .
Hypersensitivity
Vedrop, the commercial form, contains sodium methyl parahydroxybenzoate (E219) and sodium ethyl parahydroxybenzoate (E215) which may cause allergic reactions, which are sometimes delayed .
Pregnancy
There is no current data on taking tocofersolan during pregnancy. Animal studies do not indicate direct or indirect harmful effects with respect to pregnancy, embryonal/ fetal development, parturition or postnatal development. Caution should be taken when prescribing this medication to pregnant women .
Breast-feeding
It is unknown whether tocofersolan is released into human breast milk. The excretion of tocofersolan in milk has not been studied in animals .
Fertility
No data is available .

The Uses of Tocofersolan

Tocofersolan is a polyethylene glycol derivative of α-Tocopherol (T526125). Tocofersolan is a synthetic water-soluble vitamin E unlike its natural counterpart which are fat soluble. Tocofersolan is used in pediatrics in the treatment vitamin E-deficient cholestatic children. Tocofersolan has potential application as a absorption enhancer in drug delivery systems.

Background

D-Alpha-tocopheryl polyethylene glycol 1000 succinate (Tocofersolan, Vedrop), has been developed in Europe as an orally bioavailable source of vitamin E in children suffering from cholestasis . Cholestasis is the reduction or stoppage of bile flow, either to impaired secretion by hepatocytes (liver cells) or obstruction , .
Tocofersolan is a polyethylene glycol derivative of α-tocopherol and synthetic water-soluble version of Tocopherol. Tocofersolan is an oral treatment of vitamin E deficiency due to digestive malabsorption in pediatric patients with congenital chronic cholestasis or hereditary chronic cholestasis. It was approved by the European Medicines Agency (EMA) in June 2009 under the market name Vedrop. Moreover, the agent is capable of demonstrating antioxidant effects that make it a popular component to include in cosmetics and pharmaceuticals as well.
In addition to the above, tocofersolan has been studied as a promising application as an absorption enhancer in drug delivery .

Indications

Tocofersolan is indicated in vitamin E deficiency caused by digestive malabsorption in pediatric patients with congenital chronic cholestasis or hereditary chronic cholestasis from birth (full term newborns) up to 18 years of age .

Pharmacokinetics

Because of its increased solubility , , , this medication readily penetrates cells, unlike other types of vitamin E , which are strictly fat-soluble . Specific to cholestasis, tocofersolan normalizes vitamin E levels relieving the symptoms of deficiency because of its facilitation of vitamin E absorption , .

Metabolism

The hydrolysis of tocofersolan occurs in the gut lumen. Tocofersolan is absorbed by cells, and the alpha-tocopherol moiety appears in chylomicrons in the lymph system in a manner that is identical to vitamin E absorbed from dietary sources. Cellular uptake does not require receptors, binding proteins or metabolic processes and does not occur by pinocytosis. Absorption of deuterated tocofersolan demonstrated a normal pattern in lipoproteins: alpha-tocopherol peaked first in chylomicrons, then peaked in very low- density lipoproteins (VLDL) and finally in low-density lipoproteins (LDL) and high-density lipoproteins (HDL).