In zebrafish embryos exposed to BaP at a concentration of 1 μM, tocofersolan (0-3 μM) significantly attenuates BaP-induced hypoactivity and enhances locomotor activity [3].

Absorption, Distribution and Excretion
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 [DB11251].
Vitamin E is primarily eliminated in the bile (75%) and feces, either as free tocopherol or in oxidized forms. Urine is a minor elimination route of vitamin E (as glucuronic-conjugate).
Located principally on cell membranes, within mitochondria and microsomes, vitamin E is widely distributed throughout the body (red blood cells, brain, muscle, liver, platelets) and fat tissues are its primary reservoir.

---

Metabolism / Metabolites
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).

---

Biological Half-Life
29.7 h

Protein Binding
Highly bound to lipoproteins.

[1]. Antioxidant capacity in Fasciola hepatica patients before and after treatment with triclabendazole alone or in combination with ascorbic acid (vitamin C) and tocofersolan (vitamin E). Arzneimittelforschung. 2003;53(3):214-20.

[2]. Recent developments in d-α-tocopheryl polyethylene glycol-succinate-based nanomedicine for cancer therapy [published correction appears in Drug Deliv. 2017 Nov;24(1):1930]. Drug Deliv. 2017;24(1):1831-1842.

[3]. The use of tocofersolan as a rescue agent in larval zebrafish exposed to benzo[a]pyrene in early development. Neurotoxicology. 2021 Sep;86:78-84.

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 [DB11251]. 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 [MSDS].
See also: Vitamin E Polyethylene Glycol Succinate (annotation moved to).

---

Drug Indication
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.
FDA Label

---

Mechanism of Action
Vitamin E is a major lipo-soluble antioxidant in humans. It acts as a free radical chain breaking molecule, halting the peroxidation of polyunsaturated fatty acids and it plays an important role in maintaining both the stability and integrity of cell membranes.

---

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

C35H58O6

574.84

574.423

9002-96-4

59-02-9 (vitamin E);58-95-7 (acetate);17407-37-3 (Hemisuccinate);9002-96-4 (PEG 1000 succinate);

9938056

Off-white to light yellow <34°C powder,>38°C liquid

1.01g/cm3

662.7ºC at 760mmHg

34-38ºC

195.4ºC

1.496

8.388

1

6

20

41

768

3

C(=O)(OC1C(C)=C2CCC(C)(CCCC(CCCC(CCCC(C)C)C)C)OC2=C(C)C=1C)CCC(=O)OCO

AOBORMOPSGHCAX-AZAGJHQNSA-N

InChI=1S/C35H58O6/c1-24(2)12-9-13-25(3)14-10-15-26(4)16-11-20-35(8)21-19-30-29(7)33(27(5)28(6)34(30)41-35)40-32(38)18-17-31(37)39-23-22-36/h24-26,36H,9-23H2,1-8H3/t25-,26-,35-/m1/s1

D –α-TocopherolPEG 1000 succinate 2-hydroxyethyl (2,5,7,8-tetramethyl-2-(4,8,12-trimethyltridecyl)chroman-6-yl) succinate

Vitamin E-TPGSD –α-Tocopherol PEG 1000 succinate TPGS,D-α-Tocopherol polyethylene glycol succinate, Vitamin E polyethylene glycol succinate,

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

DMSO : ~100 mg/mL (~66.09 mM)
H2O : ~100 mg/mL (~66.09 mM)
Ethanol : ~50 mg/mL (~33.05 mM)

Solubility in Formulation 1: ≥ 2.5 mg/mL (1.65 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 2: ≥ 2.5 mg/mL (1.65 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

View More

Solubility in Formulation 3: ≥ 2.5 mg/mL (1.65 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly.

---

Solubility in Formulation 4: ≥ 2.5 mg/mL (1.65 mM) (saturation unknown) in 5% DMSO + 40% PEG300 + 5% Tween80 + 50% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution.

---

Solubility in Formulation 5: ≥ 2.5 mg/mL (1.65 mM) (saturation unknown) in 5% DMSO + 95% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution.
Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution.

---

Solubility in Formulation 6: 100 mg/mL (66.09 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication (<60°C).

---

 (Please use freshly prepared in vivo formulations for optimal results.)