Tocofersolan API Manufacturers

General Description:

Tocofersolan, identified by CAS number 9002-96-4, is a notable compound with significant therapeutic applications. 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 . 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:

This drug is primarily indicated for: 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 . Its use in specific medical scenarios underscores its importance in the therapeutic landscape.

Metabolism:

Tocofersolan undergoes metabolic processing primarily in: 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). This metabolic pathway ensures efficient processing of the drug, helping to minimize potential toxicity and side effects.

Absorption:

The absorption characteristics of Tocofersolan are crucial for its therapeutic efficacy: 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 . The drug's ability to rapidly penetrate into cells ensures quick onset of action.

Half-life:

The half-life of Tocofersolan is an important consideration for its dosing schedule: 29.7 h. This determines the duration of action and helps in formulating effective dosing regimens.

Protein Binding:

Tocofersolan exhibits a strong affinity for binding with plasma proteins: Highly bound to lipoproteins . This property plays a key role in the drug's pharmacokinetics and distribution within the body.

Route of Elimination:

The elimination of Tocofersolan from the body primarily occurs through: 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) . Understanding this pathway is essential for assessing potential drug accumulation and toxicity risks.

Volume of Distribution:

Tocofersolan is distributed throughout the body with a volume of distribution of: 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 . This metric indicates how extensively the drug permeates into body tissues.

Pharmacodynamics:

Tocofersolan exerts its therapeutic effects through: 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 , . The drug's ability to modulate various physiological processes underscores its efficacy in treating specific conditions.

Mechanism of Action:

Tocofersolan functions by: 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 . This mechanism highlights the drug's role in inhibiting or promoting specific biological pathways, contributing to its therapeutic effects.

Toxicity:

Categories:

Tocofersolan is categorized under the following therapeutic classes: Alimentary Tract and Metabolism, Benzopyrans, Compounds used in a research, industrial, or household setting, Cytochrome P-450 CYP3A Substrates, Cytochrome P-450 CYP3A4 Substrates, Cytochrome P-450 Substrates, Drug Carriers, Heterocyclic Compounds, Fused-Ring, Pyrans, Vitamin E, Vitamins, Vitamins (Fat Soluble). These classifications highlight the drug's diverse therapeutic applications and its importance in treating various conditions.

Experimental Properties:

Further physical and chemical characteristics of Tocofersolan include:

• Water Solubility: soluble at 1g/10 mL
• Melting Point: 34-38