TAMIPOOL FOR INJECTION

Product Information

Registration Status: Active

TAMIPOOL FOR INJECTION is approved to be sold in Singapore with effective from 2002-03-15. It is marketed by MEDIPHARM PTE LTD, with the registration number of SIN11849P.

This product contains Ascorbic Acid 100mg/vial,Biotin 60mcg/vial,Cyanocobalamin 5mcg/vial,Dexpanthenol 15mg/vial,Ergocalciferol 200 iu/vial,Folic Acid 400mcg/vial,Nicotinamide 40mg/vial,Pyridoxine 4mg/vial,Sodium Riboflavine Phosphate 3.6mg/vial,Thiamine 3mg/vial,Tocopherol Acetate 10mg/vial, and Vitamin A 3300 iu/vial in the form of INJECTION, POWDER, FOR SOLUTION. It is approved for INTRAVENOUS use.

This product is manufactured by CELLTRION PHARM in KOREA, and INC. in REPUBLIC OF.

It is an Over-the-counter Medicine that can be freely obtained from any retailer

Ascorbic Acid
Biotin
Cyanocobalamin
Dexpanthenol
Ergocalciferol
Folic Acid
Nicotinamide
Pyridoxine
Sodium Riboflavine Phosphate
Thiamine
Tocopherol Acetate
Vitamin A

Description

A six carbon compound related to glucose. It is found naturally in citrus fruits and many vegetables. Ascorbic acid is an essential nutrient in human diets, and necessary to maintain connective tissue and bone. Its biologically active form, vitamin C, functions as a reducing agent and coenzyme in several metabolic pathways. Vitamin C is considered an antioxidant.

Indication

Used to treat vitamin C deficiency, scurvy, delayed wound and bone healing, urine acidification, and in general as an antioxidant. It has also been suggested to be an effective antiviral agent.

Mechanism of Action

In humans, an exogenous source of ascorbic acid is required for collagen formation and tissue repair by acting as a cofactor in the posttranslational formation of 4-hydroxyproline in -Xaa-Pro-Gly- sequences in collagens and other proteins. Ascorbic acid is reversibly oxidized to dehydroascorbic acid in the body. These two forms of the vitamin are believed to be important in oxidation-reduction reactions. The vitamin is involved in tyrosine metabolism, conversion of folic acid to folinic acid, carbohydrate metabolism, synthesis of lipids and proteins, iron metabolism, resistance to infections, and cellular respiration.

Pharmacokinetics

Absorption
70% to 90%
Distribution
Metabolism
Hepatic. Ascorbic acid is reversibly oxidised (by removal of the hydrogen from the enediol group of ascorbic acid) to dehydroascorbic acid. The two forms found in body fluids are physiologically active. Some ascorbic acid is metabolized to inactive compounds including ascorbic acid-2-sulfate and oxalic acid.
Elimination

Active Ingredient/Synonyms

acide ascorbique | ácido ascórbico | acidum ascorbicum | acidum ascorbinicum | Ascorbate | Ascorbic Acid | Ascorbicap | Ascorbinsäure | L-(+)-ascorbic acid | L-Ascorbate | L-Ascorbic Acid | Vitamin C |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

A water-soluble, enzyme co-factor present in minute amounts in every living cell. It occurs mainly bound to proteins or polypeptides and is abundant in liver, kidney, pancreas, yeast, and milk. [PubChem]

Indication

For nutritional supplementation, also for treating dietary shortage or imbalance.

Mechanism of Action

Biotin is necessary for the proper functioning of enzymes that transport carboxyl units and fix carbon dioxide, and is required for various metabolic functions, including gluconeogenesis, lipogenesis, fatty acid biosynthesis, propionate metabolism, and catabolism of branched-chain amino acids.

Pharmacokinetics

Absorption
Systemic - approximately 50%
Distribution
Metabolism
Elimination

Toxicity

Prolonged skin contact may cause irritation.

Active Ingredient/Synonyms

(+)-cis-Hexahydro-2-oxo-1H-thieno[3,4]imidazole-4-valeric acid | (3AS,4S,6ar)-hexahydro-2-oxo-1H-thieno[3,4-D]imidazole-4-valeric acid | 5-(2-Oxohexahydro-1H-thieno[3,4-D]imidazol-4-yl)pentanoic acid | Biotin | Biotina | Biotine | Biotinum | cis-(+)-Tetrahydro-2-oxothieno[3,4]imidazoline-4-valeric acid | cis-Hexahydro-2-oxo-1H-thieno(3,4)imidazole-4-valeric acid | cis-Tetrahydro-2-oxothieno(3,4-D)imidazoline-4-valeric acid | Coenzyme R | D-(+)-Biotin | D-Biotin | D(+)-Biotin | Vitamin B7 | Vitamin H | Biotin |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

Cyanocobalamin (commonly known as Vitamin B12) is the most chemically complex of all vitamins. Its chemical structure is based on a _corrin_ ring, which, although quite similar to the porphyrin ring found in heme, chlorophyll, and cytochrome, has two of the pyrrole rings directly bonded. The central metal ion in cyanocobalamin is Co (cobalt). Cyanocobalamin (Vitamin B12) is not produced by plants or by animals. The only organisms that have the enzymes required for the synthesis of cyanocobalamin are bacteria and archaea [L2058]. Higher plants do not utilize cyanocobalamin from the soil, and are therefore a poor source of the substance as compared with animal tissues, which are potent in cyanocobalamin [L2058]. Vitamin B12 is naturally found in animal products, including fish, meat, poultry, eggs, milk, and milk products. Vitamin B12 is generally not present in plant foods, but fortified breakfast cereals are a readily available source of vitamin B12 with high bioavailability for vegetarian consumers. Various nutritional yeast products also contain vitamin B12 [L2064]. The main causes of vitamin B12 deficiency include vitamin B12 malabsorption, pernicious anemia, postsurgical malabsorption, and lastly, dietary deficiency. In many cases, however, the cause of deficiency is unknown [L2064].

Indication

For treatment of pernicious anemia (due to lack of or inhibition of intrinsic factor) and for prevention and treatment of vitamin B 12 deficiency [L2064], [L2068]. Values below approximately 170–250 pg/mL (120–180 picomol/L) for adults suggest a vitamin B12 deficiency. Despite this, evidence suggests that serum vitamin B12 concentrations may not accurately reflect intracellular concentrations of the vitamin [L2064]. It is therefore difficult to diagnose vitamin B12 deficiency.

Mechanism of Action

Vitamin B12 is used in the body in two forms: Methylcobalamin and 5-deoxyadenosyl cobalamin. The enzyme methionine synthase needs methylcobalamin as a cofactor. This enzyme is involved in the conversion of the amino acid homocysteine into methionine. Methionine, is required for DNA methylation [L2064], [L2068]. Vitamin B12 is converted to coenzyme B12 in tissues. This form is required for the conversion of methylmalonate to succinate and the synthesis of methionine from homocysteine (a reaction also requiring folate) [L2068]. Without coenzyme B12, tetrahydrofolate cannot be regenerated from its inactive storage form, _5-methyl tetrahydrofolate_, leading to functional folate deficiency. Vitamin B12 also may be involved in maintaining sulfhydryl (SH) groups in the reduced form needed by many SH-activated enzyme systems [L2068]. Via the above reactions, vitamin B12 is associated with both fat and carbohydrate metabolism, as well as protein synthesis [L2068]. _5-Deoxyadenosyl_ cobalamin is a cofactor needed by the enzyme that acts to convert _L-methylmalonyl-CoA_ to _succinyl-CoA_. This conversion is an important step in the extraction of energy from proteins and fats. Additionally, _succinyl CoA_ is necessary for the production of hemoglobin, the substance that carries oxygen in red blood cells [L2064]. _L-methylmalonyl-CoA mutase_ converts L-methylmalonyl-CoA to succinyl-CoA in the degradation of propionate, an important biochemical reaction in the metabolism of lipids and proteins. _Succinyl-CoA_ is also required for hemoglobin synthesis [L2064].

Pharmacokinetics

Absorption
Approximately 56% of a 1 mcg oral dose of vitamin B12 is absorbed, however, absorption decreases significantly when intrinsic factor capacity is exceeded (at 1–2 mcg of vitamin B12) [L2064]. Readily absorbed in the lower half of the ileum [L2067]. Bioavailability of the nasal gel vitamin B12 and spray forms compared to intramuscular injection are about 9% and 6%, respectively [L2068]. Because the intranasal forms have lower absorption than the IM dosage form, intranasal B12 forms dosed administered once weekly. After 1 month of treatment in pernicious anemia, the weekly dosing of 500 mcg B12 intranasal gel resulted in a significant increase in B12 levels in comparison to a once-monthly 100 mcg IM dose [L2068].
Distribution
Once absorbed, vitamin B12 is highly bound to transcobalamin II, a specific B-globulin carrier protein and is distributed and stored primarily in the liver as coenzyme B12 [L2068]. It has been found that the distribution of vitamin B12 is dependent on the current cobalamine status, from animal studies [L2067]. The bone marrow also stores a high amount of absorbed vitamin B12 [L2068]. This vitamin crosses the placenta and is found distributed in breast milk. Enterohepatic recirculation conserves systemic stores of Vitamin B12 [L2067].
Metabolism
Mainly Hepatic [A32397], [L2058]. Vitamin B12 serves as a cofactor for methionine synthase and _L-methylmalonyl-CoA mutase_ enyme. Methionine synthase catalyzes the conversion of homocysteine to methionine during metabolism. Methionine is necessary for the formation of S-adenosylmethionine, a universal methyl donor for about 100 substrates, including DNA, RNA, hormones, proteins, and lipids [L2064]. Vitamin B12, which is bound to protein in food, is released following the activity of hydrochloric acid and gastric protease in the stomach. When synthetic vitamin B12 is added to fortified foods and dietary supplements, it is found in the free form and, and does not require this separation step. Free vitamin B12 then binds with intrinsic factor (IF), a glycoprotein secreted by the parietal cells of the stomach, and the newly formed complex undergoes absorption within the distal ileum by receptor-mediated endocytosis [L2071]. Intestinal microorganisms produce cobalamin in the colon, however, not absorbed and thus vitamin B12 must be supplied with the food. In mammals, the assimilation and transport of dietary cobalamin is performed by three successive proteins, haptocorrin (HC), gastric intrinsic factor (IF) and transcoba- lamin. Cobalamin is required by cells for two enzyme cofactors, _methyl-Cbl_ for _methionine synthase_ and _50 -deoxyadenosyl-Cbl (Ado-Cbl)_ for _methyl- malonyl-CoA mutase_ [L2068]. In the stomach, Cobalamin is firstly bound to salivary HC. Following proteolytic cleavage of HC into 2-3 fragments in the duodenum, and is then transferred to IF. Mucosal cells in the terminal ileum absorb the IF-Cobalamin complex by a process called _endocytosis_ by the _cubilin_-amnionless receptor [L2068]. In the enterocyte (intestinal cell), Cobalamin is freed from IF and appears in the blood combined with transcobalamin which carries cobalamin to cells. Only the fraction of Cbl bound to TC is quickly taken up by endocytosis by a specific receptor of yet unknown structure, present on most cell types [L2068]. The other Cbl- transporting protein in plasma is homocysteine. Its ability to promote cellular uptake of cobalamin is found to be limited, but it is thought to serve as a storage protein as well as scavenger of inactive Cbl- analogues [L2071].
Elimination

Toxicity

Anaphylactic reactions (skin rash, itching, wheezing) post parenteral administration has occurred. The Institute of Medicine (IOM), USA, did not establish an upper limit for vitamin B12 because of its low potential for toxicity. In Dietary Reference Intakes [L2066]: Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline, the IOM declares that “no adverse effects have an association with excess vitamin B12 intake from both food and dietary supplements in healthy individuals” [L2066]. Findings from intervention trials support these conclusions. In the NORVIT and HOPE 2 trials, vitamin B12 supplementation (in combination with folic acid and vitamin B6) did not cause any serious adverse events when administered at doses of 0.4 mg for 40 months (NORVIT trial) and 1.0 mg for 5 years (HOPE 2 trial) [A32388, A32389]. Parenteral methylcobalamin is classified as pregnancy category C. Adequate studies in humans have not been conducted; however, no maternal or fetal complications have been associated with doses that are recommended during pregnancy, and appropriate treatment should not be withheld from pregnant women with vitamin B12 responsive anemias. Conversely, pernicious anemia resulting from vitamin B12 deficiency may cause infertility or poor pregnancy outcomes. Vitamin B12 deficiency has occurred in breast-fed infants of vegetarian mothers whose diets contain no animal products (e.g., eggs, dairy), even though the mothers had no symptoms of deficiency at the time. Maternal requirements for vitamin B12 increase during pregnancy [L2064].

Active Ingredient/Synonyms

Cyanocob(III)alamin | Vitamin B12 | Vitamin B12 complex | Vitamin B12 NOS | Cyanocobalamin |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

Dexpanthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol is enzymatically cleaved to form pantothenic acid, which is an essential component of Coenzyme A, which acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium[A32373]. Due to its good penetration and high local concentrations, dexpanthanol is used in many topical products, such as ointments and lotions for treatment of dermatological conditions to relieve itching or promote healing. Dermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties [A32377]. Dexpanthenol is also available as a racemic mixture containing both the dextrorotatory form (dexpanthenol) and the levorotatory form (levopanthenol) as [DB11204]. While pantothenic acid is optically active, only the dextrorotatory form (dexpanthenol) is biologically active.

Indication

Injection: Prophylactic use immediately after major abdominal surgery to minimize the possibility of paralytic ileus. Intestinal atony causing abdominal distention; postoperative or postpartum retention of flatus, or postoperative delay in resumption of intestinal motility; paralytic ileus. Topical: This medication is used as a moisturizer to treat or prevent dry, rough, scaly, itchy skin and minor skin irritations (e.g., diaper rash, skin burns from radiation therapy).

Mechanism of Action

Dexpanthenol is an alcohol derivative of pantothenic acid, a component of the B complex vitamins and an essential component of a normally functioning epithelium. Dexpanthenol is enzymatically cleaved to form pantothenic acid, which is an essential component of Coenzyme A, which acts as a cofactor in many enzymatic reactions that are important for protein metabolism in the epithelium[A32373]. Dermatological effects of the topical use of dexpanthenol include increased fibroblast proliferation and accelerated re-epithelialization in wound healing. Furthermore, it acts as a topical protectant, moisturizer, and has demonstrated anti-inflammatory properties [A32377].

Pharmacokinetics

Absorption
Dexpanthenol is soluble in water and alcohol, although insoluble in fats and oil based substances. With the appropriate vehicle, Dexpanthenol is easily penetrated into the skin. Rate of penetration and absorption is reduced when Dexpanthenol is administered as an oil/water formula.
Distribution
Dexpanthenol is readily converted to pantothenic acid which is widely distributed into body tissues, mainly as coenzyme A. Highest concentrations are found in the liver, adrenal glands, heart, and kidneys.
Metabolism
Dexpanthenol is readily converted to pantothenic acid which is widely distributed into body tissues, mainly as coenzyme A.
Elimination

Toxicity

Mouse LD50 : 9gm/kg (Intraperitoneal) Mouse: LD50 7gm/kg (Intravenous) Mouse: LD50 15gm/kg (Oral) Rabbit LD50 4gm/kg (Oral)

Active Ingredient/Synonyms

(+)-Panthenol | (2R)-2,4-dihydroxy-N-(3-hydroxypropyl)-3,3-dimethylbutanamide | Bepanthen | Bepanthene | Bepantol | D-panthenol | D-panthenol 50 | D-Pantothenol | D-Pantothenyl alcohol | D(+)-Panthenol | Pantol | Pantothenyl alcohol | Provitamin B | Dexpanthenol |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

Ergocalciferol (Vitamin D2) is a derivative of ergosterol formed by ultraviolet rays breaking of the C9-C10 bond. It differs from cholecalciferol in having a double bond between C22 and C23 and a methyl group at C24.

Indication

For use in the management of hypocalcemia and its clinical manifestations in patients with hypoparathyroidism, as well as for the treatment of familial hypophosphatemia (vitamin D resistant rickets). This drug has also been used in the treatment of nutritional rickets or osteomalacia, vitamin D dependent rickets, rickets or osteomalacia secondary to long-term high dose anticonvulsant therapy, early renal osteodystrophy, osteoporosis (in conjunction with calcium), and hypophosphatemia associated with Fanconi syndrome (with treatment of acidosis).

Mechanism of Action

Activated ergocalciferol increases serum calcium and phosphate concentrations, primarily by increasing intestinal absorption of calcium and phosphate through binding to a specific receptor in the mucosal cytoplasm of the intestine. Subsequently, calcium is absorbed through formation of a calcium-binding protein. 25-hydroxyergocalciferol is the intermediary metabolite of ergocalciferol. Although this metabolite exhibits 2–5 times more activity than unactivated ergocalciferol in curing rickets and inducing calcium absorption and mobilization (from bone) in animals, this increased activity is still insufficient to affect these functions at physiologic concentrations. Activated ergocalciferol stimulate resorption of bone and are required for normal mineralization of bone. Physiological doses of ergocalciferol also promotes calcium reabsorption by the kidneys, but the significance of this effect is not known.

Pharmacokinetics

Absorption
Readily absorbed from small intestine (proximal or distal), requires presence of bile salts.
Distribution
Metabolism
Within the liver, ergocalciferol is hydroxylated to ercalcidiol (25-hydroxyergocalciferol) by the enzyme 25-hydroxylase. Within the kidney, ercalcidiol serves as a substrate for 1-alpha-hydroxylase, yielding ercalcitriol (1,25-dihydroxyergocalciferol), the biologically active form of vitamin D2.
Elimination

Toxicity

LD50 = 23.7 mg/kg (Orally in mice); LD50 = 10 mg/kg (Orally in rats ); Nausea, vomiting and diarrhea, weight loss, irritability, weakness, fatigue, lassitude, and headache.

Active Ingredient/Synonyms

(3β,5Z,7E,22E)-9,10-secoergosta-5,7,10(19),22-tetraen-3-ol | (5Z,7E,22E)-(3S)-9,10-seco-5,7,10(19),22-ergostatetraen-3-ol | (5Z,7E,22E)-(3S)-9,10-secoergosta-5,7,10(19),22-tetraen-3-ol | Activated ergosterol | Ercalciol | Ergocalciférol | Ergocalciferol | Ergocalciferolum | Oleovitamin D2 | Viosterol | Vitamin D2 | Vitamina D2 | Ergocalciferol |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

A member of the vitamin B family that stimulates the hematopoietic system. It is present in the liver and kidney and is found in mushrooms, spinach, yeast, green leaves, and grasses (poaceae). Folic acid is used in the treatment and prevention of folate deficiencies and megaloblastic anemia. [PubChem]

Indication

For treatment of folic acid deficiency, megaloblastic anemia and in anemias of nutritional supplements, pregnancy, infancy, or childhood.

Mechanism of Action

Folic acid, as it is biochemically inactive, is converted to tetrahydrofolic acid and methyltetrahydrofolate by dihydrofolate reductase. These folic acid congeners are transported across cells by receptor-mediated endocytosis where they are needed to maintain normal erythropoiesis, synthesize purine and thymidylate nucleic acids, interconvert amino acids, methylate tRNA, and generate and use formate. Using vitamin B12 as a cofactor, folic acid can normalize high homocysteine levels by remethylation of homocysteine to methionine via methionine synthetase.

Toxicity

IPR-MUS LD50 85 mg/kg,IVN-GPG LD50 120 mg/kg, IVN-MUS LD50 239 mg/kg, IVN-RAT LD50 500 mg/kg, IVN-RBT LD50 410 mg/kg

Active Ingredient/Synonyms

Folacin | Folate | Folic acid | Folsaeure | N-[(4-{[(2-amino-4-oxo-1,4-dihydropteridin-6-yl)methyl]amino}phenyl)carbonyl]-L-glutamic acid | N-Pteroyl-L-glutamic acid | PGA | PteGlu | Pteroyl-L-glutamate | Pteroyl-L-glutamic acid | Pteroyl-L-monoglutamic acid | Pteroylglutamic acid | Vitamin B9 | Vitamin Bc | Vitamin M | Folic Acid |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

NADH is the reduced form of NAD+, and NAD+ is the oxidized form of NADH, a coenzyme composed of ribosylnicotinamide 5'-diphosphate coupled to adenosine 5'-phosphate by pyrophosphate linkage. It is found widely in nature and is involved in numerous enzymatic reactions in which it serves as an electron carrier by being alternately oxidized (NAD+) and reduced (NADH). It forms NADP with the addition of a phosphate group to the 2' position of the adenosyl nucleotide through an ester linkage. (Dorland, 27th ed)

Indication

Some evidence suggests that NADH might be useful in treating Parkinson's disease, chronic fatigue syndrome, Alzheimer's disease and cardiovascular disease.

Mechanism of Action

NADH is synthesized by the body and thus is not an essential nutrient. It does require the essential nutrient nicotinamide for its synthesis, and its role in energy production is certainly an essential one. In addition to its role in the mitochondrial electron transport chain, NADH is produced in the cytosol. The mitochondrial membrane is impermeable to NADH, and this permeability barrier effectively separates the cytoplasmic from the mitochondrial NADH pools. However, cytoplasmic NADH can be used for biologic energy production. This occurs when the malate-aspartate shuttle introduces reducing equivalents from NADH in the cytosol to the electron transport chain of the mitochondria. This shuttle mainly occurs in the liver and heart.

Pharmacokinetics

Absorption
Unclear how much of an administered dose is absorbed.
Distribution
Metabolism
Elimination

Toxicity

No reports of overdose, however, high doses of NADH (10 mg a day or more) may cause jitteriness, anxiety, and insomnia.

Active Ingredient/Synonyms

1,4-dihydronicotinamide adenine dinucleotide | DPNH | NAD reduced form | Nicotinamide adenine dinucleotide (reduced) | Nicotinamide-adenine dinucleotide, reduced | Reduced nicotinamide adenine diphosphate | Reduced nicotinamide-adenine dinucleotide | NADH |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

Pyridoxine is the 4-methanol form of vitamin B6, an important water-soluble vitamin that is naturally present in many foods. As its classification as a vitamin implies, Vitamin B6 (and pyridoxine) are essential nutrients required for normal functioning of many biological systems within the body. While many plants and microorganisms are able to synthesize pyridoxine through endogenous biological processes, animals must obtain it through their diet. More specifically, pyridoxine is converted to pyridoxal 5-phosphate in the body, which is an important coenzyme for synthesis of amino acids, neurotransmitters (serotonin, norepinephrine), sphingolipids, and aminolevulinic acid. It's important to note that Vitamin B6 is the collective term for a group of three related compounds, pyridoxine, pyridoxal, and pyridoxamine, and their phosphorylated derivatives, pyridoxine 5'-phosphate, pyridoxal 5'-phosphate and pyridoxamine 5'-phosphate. Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine [A32836]. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA) [A32837]. Pyridoxine is used medically for the treatment of vitamin B6 deficiency and for the prophylaxis of isoniazid-induced peripheral neuropathy (due to [DB00951]'s mechanism of action which competitively inhibits the action of pyridoxine in the above-mentioned metabolic functions). It is also used in combination with [DB00366] (as the commercially available product Diclectin) for the treatment of nausea and vomiting in pregnancy.

Indication

Pyridoxine is indicated for the treatment of vitamin B6 deficiency and for the prophylaxis of [DB00951]-induced peripheral neuropathy. It is also approved by Health Canada for the treatment of nausea and vomiting in pregnancy in a combination product with [DB00366] (as the commercially available product Diclectin).

Mechanism of Action

Vitamin B6 is the collective term for a group of three related compounds, pyridoxine (PN), pyridoxal (PL) and pyridoxamine (PM), and their phosphorylated derivatives, pyridoxine 5'-phosphate (PNP), pyridoxal 5'-phosphate (PLP) and pyridoxamine 5'-phosphate (PMP). Although all six of these compounds should technically be referred to as vitamin B6, the term vitamin B6 is commonly used interchangeably with just one of them, pyridoxine. Vitamin B6, principally in its biologically active coenzyme form pyridoxal 5'-phosphate, is involved in a wide range of biochemical reactions, including the metabolism of amino acids and glycogen, the synthesis of nucleic acids, hemogloblin, sphingomyelin and other sphingolipids, and the synthesis of the neurotransmitters serotonin, dopamine, norepinephrine and gamma-aminobutyric acid (GABA).

Pharmacokinetics

Absorption
The B vitamins are readily absorbed from the gastrointestinal tract, except in malabsorption syndromes. Pyridoxine is absorbed mainly in the jejunum. The Cmax of pyridoxine is achieved within 5.5 hours.
Distribution
Pyridoxine main active metabolite, pyridoxal 5’-phosphate, is released into the circulation (accounting for at least 60% of circulating vitamin B6) and is highly protein bound, primarily to albumin.
Metabolism
Pyridoxine is a prodrug primarily metabolized in the liver. The metabolic scheme for pyridoxine is complex, with formation of primary and secondary metabolites along with interconversion back to pyridoxine. Pyridoxine's major metabolite is 4-pyridoxic acid.
Elimination

Toxicity

Oral Rat LD50 = 4 gm/kg. Toxic effects include convulsions, dyspnea, hypermotility, diarrhea, ataxia and muscle weakness.

Active Ingredient/Synonyms

2-Methyl-3-hydroxy-4,5-dihydroxymethylpyridine | 3-hydroxy-4,5-bis(hydroxymethyl)-2-methylpyridine | 3-Hydroxy-4,5-dimethylol-alpha-picoline | 5-Hydroxy-6-methyl-3,4-pyridinedimethanol | Pyridoxine | Pyridoxol | Vitamin B6 | Pyridoxine |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.



Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

Thiamine or thiamin, also known as vitamin B1, is a colorless compound with the chemical formula C12H17N4OS. It is soluble in water and insoluble in alcohol. Thiamine decomposes if heated. Thiamine was first discovered by Umetaro Suzuki in Japan when researching how rice bran cured patients of Beriberi. Thiamine plays a key role in intracellular glucose metabolism and it is thought that thiamine inhibits the effect of glucose and insulin on arterial smooth muscle cell proliferation. Thiamine plays an important role in helping the body convert carbohydrates and fat into energy. It is essential for normal growth and development and helps to maintain proper functioning of the heart and the nervous and digestive systems. Thiamine cannot be stored in the body; however, once absorbed, the vitamin is concentrated in muscle tissue.

Indication

For the treatment of thiamine and niacin deficiency states, Korsakov's alcoholic psychosis, Wernicke-Korsakov syndrome, delirium, and peripheral neuritis.

Mechanism of Action

It is thought that the mechanism of action of thiamine on endothelial cells is related to a reduction in intracellular protein glycation by redirecting the glycolytic flux. Thiamine is mainly the transport form of the vitamin, while the active forms are phosphorylated thiamine derivatives. There are five known natural thiamine phosphate derivatives: thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and the recently discovered adenosine thiamine triphosphate (AThTP), and adenosine thiamine diphosphate. Each derivative has unique functions, however, most are involved as coenzymes.

Pharmacokinetics

Absorption
Absorbed mainly from duodenum, by both active and passive processes
Distribution
Metabolism
Hepatic
Elimination

Toxicity

Thiamine toxicity is uncommon; as excesses are readily excreted, although long-term supplementation of amounts larger than 3 gram have been known to cause toxicity. Oral mouse LD50 = 8224 mg/kg, oral rat LD50 = 3710 mg/kg.

Active Ingredient/Synonyms

Aneurin | Antiberiberi factor | Thiamin | thiamine | thiamine(1+) | thiamine(1+) ion | thiaminium | tiamina | Vitamin B1 | Thiamine |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

Alpha-tocopherol is the primary form of vitamin E that is preferentially used by the human body to meet appropriate dietary requirements. In particular, the RRR-alpha-tocopherol (or sometimes called the d-alpha-tocopherol stereoisomer) stereoisomer is considered the natural formation of alpha-tocopherol and generally exhibits the greatest bioavailability out of all of the alpha-tocopherol stereoisomers. Moreover, RRR-alpha-tocopherol acetate is a relatively stabilized form of vitamin E that is most commonly used as a food additive when needed [A32451]. Alpha-tocopherol acetate is subsequently most commonly indicated for dietary supplementation in individuals who may demonstrate a genuine deficiency in vitamin E. Vitamin E itself is naturally found in various foods, added to others, or used in commercially available products as a dietary supplement. The recommended dietary allowances (RDAs) for vitamin E alpha-tocopherol are: males = 4 mg (6 IU) females = 4 mg (6 IU) in ages 0-6 months, males = 5 mg (7.5 IU) females = 5 mg (7.5 IU) in ages 7-12 months, males = 6 mg (9 IU) females = 6 mg (9 IU) in ages 1-3 years, males = 7 mg (10.4 IU) females = 7 mg (10.4 IU) in ages 4-8 years, males = 11 mg (16.4 IU) females = 11 mg (16.4 IU) in ages 9-13 years, males = 15 mg (22.4 IU) females = 15 mg (22.4 IU) pregnancy = 15 mg (22.4 IU) lactation = 19 mg (28.4 IU) in ages 14+ years [L2120]. Most individuals obtain adequate vitamin E intake from their diets; genuine vitamin E deficiency is considered to be rare. Nevertheless, vitamin E is known to be a fat-soluble antioxidant that has the capability to neutralize endogenous free radicals. This biologic action of vitamin E consequently continues to generate ongoing interest and study in whether or not its antioxidant abilities may be used to help assist in preventing or treating a number of different conditions like cardiovascular disease, ocular conditions, diabetes, cancer and more. At the moment however, there exists a lack of formal data and evidence to support any such additional indications for vitamin E use.

Indication

The primary health-related use for which alpha-tocopherol acetate is formally indicated is as a dietary supplement for patients who demonstrate a genuine vitamin E deficiency. At the same time, vitamin E deficiency is generally quite rare but may occur in premature babies of very low birth weight (< 1500 grams), individuals with fat-malabsorption disorders (as fat is required for the digestive tract to absorb vitamin E), or individuals with abetalipoproteinemia - a rare, inherited disorder that causes poor absorption of dietary fat - who require extremely large doses of supplemental vitamin E daily (around 100 mg/kg or 5-10 g/day) [L2120]. In all such cases, alpha-tocopherol is largely the preferred form of vitamin E to be administered. Elsewhere, vitamin E's chemical profile as a fat-soluble antioxidant that is capable of neutralizing free radicals in the body continues to generate ongoing interest and study regarding how and whether or not the vitamin can help prevent or delay various chronic diseases associated with free radicals or other potential biological effects that vitamin E possesses like cardiovascular diseases, diabetes, ocular conditions, immune illnesses, cancer, and more [T166]. None of these ongoing studies have yet to elucidate any formally significant evidence, however [T166].

Mechanism of Action

Vitamin E's antioxidant capabilities are perhaps the primary biological action associated with alpha-tocopherol. In general, antioxidants protect cells from the damaging effects of free radicals, which are molecules that consist of an unshared electron [L2120]. These unshared electrons are highly energetic and react rapidly with oxygen to form reactive oxygen species (ROS) [L2120]. In doing so, free radicals are capable of damaging cells, which may facilitate their contribution to the development of various diseases [L2120]. Moreover, the human body naturally forms ROS when it converts food into energy and is also exposed to environmental free radicals contained in cigarette smoke, air pollution, or ultraviolet radiation from the sun [L2120]. It is believed that perhaps vitamin E antioxidants might be able to protect body cells from the damaging effects of such frequent free radical and ROS exposure [L2120]. Specifically, vitamin E is a chain-breaking antioxidant that prevents the propagation of free radical reactions [T166]. The vitamin E molecule is specifically a peroxyl radical scavenger and especially protects polyunsaturated fatty acids within endogenous cell membrane phospholipids and plasma lipoproteins [T166]. Peroxyl free radicals react with vitamin E a thousand times more rapidly than they do with the aforementioned polyunsaturated fatty acids [T166]. Furthermore, the phenolic hydroxyl group of tocopherol reacts with an organic peroxyl radical to form an organic hydroperoxide and tocopheroxyl radical [T166]. This tocopheroxyl radical can then undergo various possible reactions: it could (a) be reduced by other antioxidants to tocopherol, (b) react with another tocopheroxyl radical to form non-reactive products like tocopherol dimers, (c) undergo further oxidation to tocopheryl quinone, or (d) even act as a prooxidant and oxidize other lipids [T166]. In addition to the antioxidant actions of vitamin E, there have been a number of studies that report various other specific molecular functions associated with vitamin E [T166]. For example, alpha-tocopherol is capable of inhibiting protein kinase C activity, which is involved in cell proliferation and differentiation in smooth muscle cells, human platelets, and monocytes [T166]. In particular, protein kinase C inhibition by alpha-tocopherol is partially attributable to its attenuating effect on the generation of membrane-derived dialglycerol, a lipid that facilitates protein kinase C translocation, thereby increasing its activity [T166]. In addition, vitamin E enrichment of endothelial cells downregulates the expression of intercellular cell adhesion molecule (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1), thereby decreasing the adhesion of blood cell components to the endothelium [T166]. Vitamin E also upregulates the expression of cytosolic phospholipase A2 and cyclooxygenase-1 [T166]. The increased expression of these two rate-limiting enzymes in the arachidonic acid cascade explains the observation that vitamin E, in a dose-dependent fashion, enhanced the release of prostacyclin, a potent vasodilator and inhibitor of platelet aggregation in humans [T166]. Furthermore, vitamin E can inhibit platelet adhesion, aggregation, and platelet release reactions [T166]. The vitamin can also evidently inhibit the plasma generation of thrombin, a potent endogenous hormone that binds to platelet receptors and induces aggregation of platelets [T166]. Moreover, vitamin E may also be able to decrease monocyte adhesion to the endothellium by downregulating expression of adhesion molecules and decreasing monocyte superoxide production [T166]. Given these proposed biological activities of vitamin E, the substance continues to generate ongoing interest and studies in whether or not vitamin E can assist in delaying or preventing various diseases with any one or more of its biologic actions. For instance, studies continue to see whether vitamin E's ability to inhibit low-density lipoprotein oxidation can aid in preventing the development of cardiovascular disease or atherogenesis [T166]. Similarly, it is also believed that if vitamin E can decrease the chance of cardiovascular disease then it can also decrease the chance of related diabetic disease and complications [T166]. In much the same way, it is also believed that perhaps the antioxidant abilities of vitamin E can neutralize free radicals that are constantly reacting and damaging cellular DNA [T166]. Furthermore, it is also believed that free radical damage does contribute to protein damage in the ocular lens - another free radical-mediated condition that may potentially be prevented by vitamin E use [T166]. Where it is also suggested that various central nervous system disorders like Parkinson's disease, Alzheimer's disease, Down's syndrome, and Tardive Dyskinesia possess some form of oxidative stress component, it is also proposed that perhaps vitamin E use could assist with its antioxidant action [T166]. There have also been studies that report the possibility of vitamin E supplementation can improve or reverse the natural decline in cellular immune function in healthy, elderly individuals [T166]. As of this time however, there is either only insufficient data or even contradicting data (where certain doses of vitamin E supplementation could even potentially increase all-cause mortality) [A237] on which to suggest the use of vitamin E could formally benefit in any of these proposed indications.

Pharmacokinetics

Absorption
When vitamin E is ingested, intestinal absorption plays a principal role in limiting its bioavailability [A32451]. It is known that vitamin E is a fat-soluble vitamin that follows the intestinal absorption, hepatic metabolism, and cellular uptake processes of other lipophilic molecules and lipids [A32451]. The intestinal absorption of vitamin E consequently requires the presence of lipid-rich foods [A32451]. In particular, stable alpha-tocopherol acetate undergoes hydrolysis by bile acid-dependant lipase in the pancreas or by an intestinal mucosal esterase [A32451]. Subsequent absorption in the duodenum occurs by way of transfer from emulsion fat globules to water-soluble multi- and unilamellar vesicles and mixed micelles made up of phospholipids and bile acids [A32451]. As the uptake of vitamin E into enterocytes is less efficient compared to other types of lipids, this could potentially explain the relatively low bioavailability of vitamin E [A32451]. Alpha-tocopherol acetate itself is embedded in matrices where its hydrolysis and its uptake by intestinal cells are markedly less efficient than in mixed micelles [A32451]. Subsequently, the intestinal cellular uptake of vitamin E from mixed micelles follows in principle two different pathways across enterocytes: (a) via passive diffusion, and (b) via receptor-mediated transport with various cellular transports like scavenger receptor class B type 1, Niemann-Pick C1-like protein, ATP-binding cassette (ABC) transporters ABCG5/ABCG8, or ABCA1, among others [A32451]. Vitamin E absorption from the intestinal lumen is dependent upon biliary and pancreatic secretions, micelle formation, uptake into enterocytes, and chylomicron secretion [T166]. Defects at any step can lead to impaired absorption. [T166]. Chylomicron secretion is required for vitamin E absorption and is a particularly important factor for efficient absorption. All of the various vitamin E forms show similar apparent efficiencies of intestinal absorption and subsequent secretion in chylomicrons [T166]. During chylomicron catabolism, some vitamin E is distributed to all the circulating lipoproteins [T166]. Chylomicron remnants, containing newly absorbed vitamin E, are then taken up by the liver [T166]. Vitamin E is secreted from the liver in very low density lipoproteins (VLDLs). Plasma vitamin E concentrations depend upon the secretion of vitamin E from the liver, and only one form of vitamin E, alpha-tocopherol, is ever preferentially resecreted by the liver [T166]. The liver is consequently responsible for discriminating between tocopherols and the preferential plasma enrichment with alpha-tocopherol [T166]. In the liver, the alpha-tocopherol transfer protein (alpha-TTP) likely is in charge of the discriminatory function, where RRR- or d-alpha-tocopherol possesses the greatest affinity for alpha-TTP [T166]. It is nevertheless believed that only a small amount of administered vitamin E is actually absorbed. In two individuals with gastric carcinoma and lymphatic leukemia, the respective fractional absorption in the lymphatics was only 21 and 29 percent of label from meals containing alpha-tocopherol and alpha-tocopheryl acetate, respectively [T166]. Additionally, after feeding three separate single doses of 125 mg, 250 mg, and 500 mg to a group of healthy males, the observed plasma peak concentrations (ng/mL) were 1822 +/- 48.24, 1931.00 +/- 92.54, and 2188 +/- 147.61, respectively [L2268].
Distribution
When three particular doses alpha-tocopherol were administered to healthy male subjects, the apparent volumes of distribution (ml) observed were: (a) at a single administered dose of 125 mg, the Vd/f was 0.070 +/- 0.002, (b) at dose 250. mg, the Vd/f was 0.127 +/- 0.004, and (c) at dose 500 mg, the Vd/f was 0.232 +/- 0.010 [L2268].
Metabolism
Primary hepatic metabolism of alpha-tocopherol begins in the endoplasmic reticulum with CYP4F2/CYP3A4 dependent ω-hydroxylation of the aliphatic side-chain, which forms the 13’-hydroxychromanol (13’-OH) metabolite [A32451]. Next, peroxisome ω-oxidation results in 13’-carboxychromanol (13’-COOH) [A32451]. Following these two steps are five consecutive β-oxidation reactions which serve to shorten the alpha-tocopherol metabolite side-chains [A32451]. The first of these β-oxidations occurs still in the peroxisome environment, generating carboxydimethyldecylhydroxychromanol (CDMDHC, 11’-COOH) [A32451]. Then, in the mitochondrion, the second β-oxidation step forms the carboxymethyloctylhydroxychromanol (CDMOHC, 9’-COOH) metabolite [A32451]. Since both CDMDHC and CDMOHC possess a side-chain length of between 13 to 9 carbon units, they are considered long-chain metabolites. The hydrophobicity of these long-chain metabolites means they are not excreted in the urine but have been found in human microsomes, serum, and feces [A32451]. The next two β-oxidation reactions, still within the mitochondrion environment, produce two intermediate chain metabolites: carboxymethylhexylhydroxychromanol (CDMHHC, 7’-COOH), followed by carboxymethylbutylhydroxychromanol (CMBHC, 5’-COOH) [A32451]. Both of these intermediate chain metabolites are found in human plasma, feces, and urine [A32451]. Finally, the last mitochrondrion β-oxidation generates the catabolic end product of alpha-tocopherol metabolism: carboxyethyl-hydroxychromans (CEHC, 3'-COOH), which is considered a short-chain metabolite [A32451]. CEHC has been observed in human plasma, serum, urine, and feces [A32451].
Elimination

Clearance

When three specific doses of 125 mg, 250 mg, and 500 mg of alpha-tocopherol were administered as single doses to a group of healthy males, the resultant times of clearance observed, respectively, were: 0.017 +/- 0.015 l/h, 0.011 +/- 0.001 l/h, and 0.019 +/- 0.001 l/h [L2268].

Toxicity

Tocopherols are considered as non-toxic but if very high doses (approximately >2 g/kg/day) are administered, there are reports of hemorrhagic activity [A32461]. Reproductive and developmental toxicity tests are negative [A32461]. These negative results were also observed in the analysis of mutagenicity and carcinogenicity [A32461]. The majority of these tests were animal feeding studies [A32461].

Active Ingredient/Synonyms

DL-alpha tocopherol acetate | DL-alpha tocopheryl acetate | Tocopherol acetate | Tocopherol acetate, unspecified | Tocopheryl acetate | Vitamin E (alpha tocopherol acetate) | Vitamin E acetate | Vitamin E acetate, unspecified form | alpha-Tocopherol acetate |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.


Description

Retinol and derivatives of retinol that play an essential role in metabolic functioning of the retina, the growth of and differentiation of epithelial tissue, the growth of bone, reproduction, and the immune response. Dietary vitamin A is derived from a variety of carotenoids found in plants. It is enriched in the liver, egg yolks, and the fat component of dairy products. [PubChem]

Indication

For the treatment of vitamin A deficiency.

Mechanism of Action

Vision:Vitamin A (all-trans retinol) is converted in the retina to the 11-cis-isomer of retinaldehyde or 11-cis-retinal. 11-cis-retinal functions in the retina in the transduction of light into the neural signals necessary for vision. 11-cis-retinal, while attached to opsin in rhodopsin is isomerized to all-trans-retinal by light. This is the event that triggers the nerve impulse to the brain which allows for the perception of light. All-trans-retinal is then released from opsin and reduced to all-trans-retinol. All-trans-retinol is isomerized to 11-cis-retinol in the dark, and then oxidized to 11-cis-retinal. 11-cis-retinal recombines with opsin to re-form rhodopsin. Night blindness or defective vision at low illumination results from a failure to re-synthesize 11-cis retinal rapidly.
Epithelial differentiation: The role of Vitamin A in epithelial differentiation, as well as in other physiological processes, involves the binding of Vitamin A to two families of nuclear retinoid receptors (retinoic acid receptors, RARs; and retinoid-X receptors, RXRs). These receptors function as ligand-activated transcription factors that modulate gene transcription. When there is not enough Vitamin A to bind these receptors, natural cell differentiation and growth are interrupted.

Pharmacokinetics

Absorption
Readily absorbed from the normal gastrointestinal tract
Distribution
Metabolism
Hepatic. Retinol is conjugated with glucuronic acid; the B-glucuronide undergoes enterohepatic circulation and oxidation to retinol and retinoic acid. Retinoic acid undergoes decarboxylation and conjugation with glucuronic acid.
Elimination

Toxicity

Acute toxicity (single ingestion of 7 500 RE or 25 000 IU per kg or more): Signs and symptoms may be delayed for 8 to 24 hours and include: increased intracranial pressure, headache, irritability, drowsiness, dizziness, lethargy, vomiting, diarrhea, bulging of fontanels in infants, diplopia, papilledema. Peeling of skin around mouth may be observed from 1 to several days after ingestion and may spread to the rest of the body. Chronic, excessive ingestion (1 200 RE or 4 000 IU/kg daily for 6 to 15 months) may produce symptoms of pseudotumor cerebri, anorexia, weakness, arthralgias, bone pain, bone demineralization, dry skin, cracked lips, brittle nails, hair loss, splenomegaly, hepatomegaly, hypoplastic anemia, leukopenia, optic neuropathy, and blindness. Increased plasma concentrations of vitamin A occur but do not necessarily correlate with toxicity.

Active Ingredient/Synonyms

(2E,4E,6E,8E)-3,7-dimethyl-9-(2,6,6-trimethylcyclohex-1-en-1-yl)nona-2,4,6,8-tetraen-1-ol | all-trans-retinol | all-trans-retinyl alcohol | all-trans-vitamin A alcohol | Retinol | Vitamin A1 | Vitamin A |


Source of information: Drugbank (External Link). Last updated on: 3rd July 18. *Trade Name used in the content below may not be the same as the HSA-registered product.

References

  1. Health Science Authority of Singapore - Reclassified POM
  2. Drugbank