3-[(4-Amino-2-methyl-5-pyrimidinyl)methyl]-5-(2-hydroxyethyl)-4-methylthiazolium

265.354

265.111755

200-425-3

4ABT0J945J

DTXSID50220251

Crystals from water

A - Alimentary tract and metabolism

2936220000

104.15000

1.18890

Solid

250ºC (dec.)(lit.)

500.0 mg/mL

The drug is not highly susceptible to atmospheric oxidation but should be protected from air and light. Thiamine hydrochloride tablets should be stored in tight, light-resistant containers at a temperature less than 40 degrees C, preferably between 15-30 degrees C. Thiamine hydrochloride injection should be protected from light and stored at a temperature less than 40 degrees C, preferably between 15-30 degrees C; freezing should be avoided.

1.8X10-10 mm Hg at 25 deg C (est)

SLIGHT, CHARACTERISTIC

162.4 Ų [M+H]+ [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|160.3 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]|159 Ų [M]+ [CCS Type: TW, Method: calibrated with polyalanine]|162.8 Ų [M]+ [CCS Type: DT, Method: single field calibrated with ESI Low Concentration Tuning Mix (Agilent)]|155.9 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]|163 Ų [M*]+

Monoclinic plates in rosette-like clusters. Slight thiazole odor; bitter taste; decomposes at 248 °C. One gram dissolves in approximately 1 mL water, 18 mL glycerol, 100 mL 95% alcohol, 315 mL absolute alcohol; more soluble in methanol. Soluble in propylene glycol. Practically insoluble in ether, benzene, hexane, chloroform. pH of 1% wt/vol solution in water 3.13; pH of 0.1% wt/vol solution in water 3.58. On exposure to air of average humidity, the vitamin absorbs an amount of water corresponding to nearly one mole, forming a hydrate.|HYGROSCOPIC; NUT-LIKE ODOR /HYDROCHLORIDE/|READILY SPLIT BY SULFITE INTO ITS PYRIMIDINE & THIAZOLE CONSTITUENTS|Crystals. MP: 196-200 °C, decomposes; practically nonhygroscopic; pKa = 4.9. Solubility in water (g/100 mL): 2.7 (25 °C); approximately 30 (100 °C). pH of 2% aqueous solution 6.5 to 7.1, more stable than the hydrochloride; suitable for enrichment of flours and feeds, multivitamin preparations /Mononitrate/|SMALL WHITE CRYSTALS OR CRYSTALLINE POWDER /HYDROCHLORIDE/|Thiamine hydrochloride in the dry state is stable. Acidic solutions having a pH below 5.5 preferably from 5.0 to 3.5 are also relatively stable. Alkalies destroy it. It is precipitated from solution by several of the alkaloidal reagents such as mercuric chloride, iodine, picric acid, tannin, and Mayer's reagent. It is sensitive to both oxidizing and reducing agents. /Hydrochloride/|For more Other Experimental Properties (Complete) data for Vitamin B1 (6 total), please visit the HSDB record page.

1

S22-S24/25

Degradation during operations requiring heat depends on pH, oxygen content, and other factors

SRP: Criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices.

NAS, Food and Nutrition Board, Institute of Medicine; Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline. National Academy Press, Washington, D.C. (1998).[Available from, as of March 2, 2010: http://www.nap.edu/catalog/6015.html]

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.

... High dietary levels of thiamine hydrochloride have been reported to depress the metabolism of zoxazolamine and aminopyrine in rats without significantly altering the oxidative metabolism of hexobarbitone. /Thiamine hydrochloride/|In rats treated with PCB, vitamin B1 levels in blood, liver, and sciatic nerve decreased, transketolase activity decreased, and pyrophosphate effect increased. In DDT-treated rats, vitamin B1 levels decreased in blood, brain, and liver, as did transketolase activity, while pyrophosphate effect increased.|Although the clinical importance is unknown, thiamine reportedly may enhance the effect of neuromuscular blocking agents.|... Alcohol inhibits absorption of thiamine.|For more Interactions (Complete) data for Vitamin B1 (9 total), please visit the HSDB record page.

LD50 Rat sc 560 mg/kg|LD50 Rat iv 188 mg/kg|LD50 Mouse sc 301 mg/kg|LD50 Mouse iv 83 mg/kg

90-94%

Vitamin B1 is found in all plants and animals; however, most organisms contain only low concentrations(1,2). It is found intracellularly in microorganisms, in plants (although unevenly distributed), and in tissue of animals, with the highest amounts occurring in the heart, kidney, liver, and brain(1). In plants, vitamin B1 occurs predominantly as free thiamine and in animals it occurs almost entirely in phophorylated forms, mainly thiamine pyrophosphate(2). It is biosynthesized by microorganisms and plants. Dietary sources include whole grains, meat products, vegetables, milk, legumes and fruit. Vitamin B1 is also present in rice husks and yeast(3).

Dietary Sources of Vitamin B1(1). [Table#840]|Whole grain cereals, legumes such as beans and lentils, nuts, lean pork and yeast are rich sources of vitamin B1(1). [Table#841]

Vitamin B1 concentration range of 18.2 to 212.1 ug/L was reported in breast milk samples from Manila in a 1962 study of apparently healthy mothers. In another study, the mean vitamin B1 content of breast milk in women from India, Thailand, and the US was 153, 93-149, and 142 ug/L, respectively(1).

NIOSH (NOES Survey 1981-1983) has statistically estimated that 18,939 workers (9.502 of these were female) were potentially exposed to vitamin B1 in the US(1).

Vitamin B1 concentration in a typical healthy human body is approximately 30 mg of vitamine B1 in all forms with about 40-50% of this being in the muscles. Normal human blood contains about 90 ng/mL(1).|Vitamin B1 occurs in the human body as free thiamine and as thiamine monophosphate, thiamine triphosphate, and thiamine pyrophosphate. Beriberi is the disease resulting from severe thiamine deficiency; inadequate consumption of thiamine is the main cause of thiamine deficiency in underdeveloped countries. Alcoholism is the primary cause of thiamine deficiency in industrialized countries. Conditions resulting in an increased need for thiamine include strenuous physical exertion, fever, pregnancy, breast-feeding, and adolescent growth. Certain plants contain anti-thiamine factors which react with thiamine to form an oxidized, inactive product. Consuming large amounts of tea and coffee (including decaffeinated) have been associated with thiamine depletion in humans. Habitual consumption of raw freshwater fish, raw shellfish and ferns increase the risk of thiamine deficiency(1).

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

Thiamine is used to prevent and to treat thiamine deficiency syndromes including beriberi, Wernicke's encephalopathy syndrome, delirium, and peripheral neuritis associated with pellagra or neuritis of pregnancy (if associated with severe vomiting).|Although thiamine has not been shown by well-controlled trials to have any therapeutic value, the drug has been used for the management of poor appetite, ulcerative colitis, chronic diarrhea, other GI disorders, and the cerebellar syndrome. Thiamine has also been used orally as an insect repellent, but there is a lack of adequate evidence to establish the efficacy of thiamine for this use.|Low plasma thiamine concentrations have been found in patients with type 1 and type 2 diabetes mellitus. In a small placebo-controlled study, benfotiamine /a related vitamin B1 substance/ 100 mg given four times daily by mouth significantly improved neuropathic pain in patients with diabetic polyneuropathy. /Benfotiamine/|/This study assessed/ the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe congestive heart failure (CHF) who had received furosemide in doses of 80 mg/d or more for at least 3 months. PATIENTS AND METHODS: Thirty patients were randomized to 1 week of double-blind inpatient therapy with either iv thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography. RESULTS: TPPE, diuresis, and LVEF were unchanged with iv placebo. After iv thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/- 800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01). CONCLUSIONS: Thiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving longterm furosemide therapy.|For more Therapeutic Uses (Complete) data for Vitamin B1 (11 total), please visit the HSDB record page.

Serious hypersensitivity/anaphylactic reactions can occur, especially after repeated administration. Deaths have resulted from IV or IM administration of thiamine.|Anaphylaxis as an adverse systemic reaction to thiamine (vitamin B1) has been described in the literature since 1938. Although its precise mechanism is still uncertain, the reaction appears to involve immediate type hypersensitivity and to be exclusively related to parenteral administration...|Anaphylaxis. There have been occasional reports of serious and even fatal responses to the parenteral administration of thiamin. The clinical characteristics have strongly suggested an anaphylactic reaction. Symptoms associated with thiamin-induced anaphylaxis include anxiety, pruritus, respiratory distress, nausea, abdominal pain, and shock, sometimes progressing to death.|Adverse reactions with thiamine are rare, but hypersensitivity reactions have occurred, mainly after parenteral doses. These reactions have ranged in severity from very mild to, very rarely, fatal anaphylactic shock ... The UK Committee on Safety of Medicines had received, between 1970 and July, 1988, 90 reports of adverse reactions associated with the use of an injection containing high doses of vitamins B and C. The most frequent reactions were anaphylaxis (41 cases, including 2 fatalities), dyspnea or bronchospasm (13 cases), and rash or flushing (22 cases); 78 of the reactions occurred during, or shortly after, intravenous injection and the other 12 after intramuscular injectdion. They recommended that parenteral treatment be used only when essential, and that, when given, facilities for treating anaphylaxis should be available. They also recommended that, when the intravenous route was used, the injection be given slowly (over 10 minutes). Various authors have noted that parenteral treatment is essential for the prophylaxis and treatment of Wernicke's encephalopathy. However, further reports of anaphylaxis to parenteral thiamine have since been described, including one with a fatal outcome.|For more Drug Warnings (Complete) data for Vitamin B1 (15 total), please visit the HSDB record page.

Thiamine is a vitamin with antioxidant, erythropoietic, cognition-and mood-modulatory, antiatherosclerotic, putative ergogenic, and detoxification activities. Thiamine has been found to protect against lead-induced lipid peroxidation in rat liver and kidney. Thiamine deficiency results in selective neuronal death in animal models. The neuronal death is associated with increased free radical production, suggesting that oxidative stress may play an important early role in brain damage associated with thiamine deficiency. 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. Inhibition of endothelial cell proliferation may also promote atherosclerosis. Endothelial cells in culture have been found to have a decreased proliferative rate and delayed migration in response to hyperglycemic conditions. Thiamine has been shown to inhibit this effect of glucose on endothelial cells.

A group of water-soluble vitamins, some of which are COENZYMES. (See all compounds classified as Vitamin B Complex.)

Absorbed mainly from duodenum, by both active and passive processes|Absorption of thiamin occurs mainly in the jejunum. At low concentrations of thiamin, absorption occurs by an active transport system that involves phosphyrylation; at higher concentrations, absorption occurs by passive diffusion. Only a small percentage of a high dose of thiamin is absorbed, and elevated serum values result in active urinary excretion of the vitamin.|Thiamin is transported in blood in both erythrocytes and plasma and is excreted in the urine.|Thiamine is absorbed from the small intestine and is phosphorylated in the intestinal mucosa.|The B vitamins are readily absorbed from the gastrointestinal tract, except in malabsorption syndromes. Thiamine is absorbed mainly in the duodenum.|For more Absorption, Distribution and Excretion (Complete) data for Vitamin B1 (8 total), please visit the HSDB record page.

Hepatic|Converted in vivo to thiamine diphosphate, a coenzyme in the decarboxylation of alpha-keto acids.|Compound 3-(2'-methyl-4'-amino-5'-pyrimidylmethyl)-4-methylthiazole-5-acetic acid, ie thiamine acetic acid, 2-methyl-4-amino-5-formylaminomethylpyrimidine, and 5-(2-hydroxyethyl)-4-methylthiazole have been identified as important metabolites of thiamine, vitamin B1.|Biotransformation of thiamine in mammals is generally supposed to /yield/ thiochrome, thiamine disulfide, 5-(2-hydroxyethyl)-4-methyl-thiazole, and some form corresponding to pyrimidine residue of thiamine.|Thiamine is metabolized in the liver of animals. Several urinary metabolites of thiamine have been identified in humans. Little or no unchanged thiamine is excreted in urine following administration of physiologic doses; however, following administration of larger doses, both unchanged thiamine and metabolites are excreted after tissue stores become saturated.

The biological half-life of the vitamin is in the range of 9-18 days.|With higher pharmacological levels, namely repetitive 250-mg amounts taken orally and 500 mg given intramuscularly, nearly 1 week was required for steady state plasma concentrations to be reached; a mean elimination half-life of 1.8 days was estimated.|Total thiamin content of the adult human has been estimated to be approximately 30 mg, and the biological half-life of the vitamin is probably in the range of 9 to 18 days.

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. Natural derivatives of thiamine phosphate, such as thiamine monophosphate (ThMP), thiamine diphosphate (ThDP), also sometimes called thiamine pyrophosphate (TPP), thiamine triphosphate (ThTP), and thiamine triphosphate (AThTP), that act as coenzymes in addition to their each unique biological functions.|Metabolic control analysis predicts that stimulators of transketolase enzyme synthesis such as thiamin (vitamin B-1) support a high rate of nucleic acid ribose synthesis necessary for tumor cell survival, chemotherapy resistance, and proliferation. Metabolic control analysis also predicts that transketolase inhibitor drugs will have the opposite effect on tumor cells. This may have important implications in the nutrition and future treatment of patients with cancer.

Heavy metals: not more than 10 mg/kg; water: not more than 5%.

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on the left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/|/SRP:/ Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 mL/kg up to 200 mL of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/|/SRP:/ Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

/SIGNS AND SYMPTOMS/ Adverse reactions with thiamine are rare, but hypersensitivity reactions have occurred, mainly after parenteral doses. These reactions have ranged in severity from very mild to, very rarely, fatal anaphylactic shock ... The UK Committee on Safety of Medicines had received, between 1970 and July, 1988, 90 reports of adverse reactions associated with the use of an injection containing high doses of vitamins B and C. The most frequent reactions were anaphylaxis (41 cases, including 2 fatalities), dyspnea or bronchospasm (13 cases), and rash or flushing (22 cases); 78 of the reactions occurred during, or shortly after, intravenous injection and the other 12 after intramuscular injection.|/SIGNS AND SYMPTOMS/ Serious hypersensitivity/anaphylactic reactions can occur, especially after repeated administration. Deaths have resulted from IV or IM administration of thiamine.|/SIGNS AND SYMPTOMS/ Anaphylaxis. There have been occasional reports of serious and even fatal responses to the parenteral administration of thiamin. The clinical characteristics have strongly suggested an anaphylactic reaction. Symptoms associated with thiamin-induced anaphylaxis include anxiety, pruritus, respiratory distress, nausea, abdominal pain, and shock, sometimes progressing to death.|/SIGNS AND SYMPTOMS/ Allergic Sensitivity and Pruritus. One case of pruritus after an intake of 500 mg/day of thiamin intramuscularly /was reported/. Another study, which involved intravenous administration of 100 mg of thiamin hydrochloride to 989 patients, reported a burning effect at the injection site in 11 patients and pruritus in 1 patient. No reports of pruritus after thiamin ingestion were found.|For more Human Toxicity Excerpts (Complete) data for Vitamin B1 (13 total), please visit the HSDB record page.

Aneurin

100% in prevention and treatment of vitamin B1 deficiency (1975)

Bulk Powder, Oral: Tablets: 25 mg, 50 mg, 100 mg, 250 mg, 500 mg. Parenteral Injection: 100 mg/mL. NOTE: Available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name.

Most of the thiamine commercialy available is synthetic|Biosynthesized by microorganisms and plants. Dietary sources include whole grains, meat products, vegetables, milk, legumes and fruit. Also present in rice husks and yeast.

AOAC Method 986.27- Fluorometric Method. The thiamine content of the sample is estimated by oxidizing thiamine to thiochrome and measuring fluorescence. Intensity of fluorescence is proportional to thiamine concentration.|AOAC Method 953.17- Thiamine in Grain Products and Method 957.17-Thiamine in Bread. Thiamine is oxidized to thiochrome and the fluorescence measured.|THE SPECIFIC THIOCHROME FLUORESCENCE ASSAY FOR THIAMINE WAS MODIFIED TO HANDLE MICROSAMPLES & TO USE 35S-THIAMINE LIQ SCINTILLATION ASSAY.|HIGH-PRESSURE LIQ CHROMATOGRAPHY PROCEDURE FOR SIMULTANEOUS DETERMINATION OF THIAMINE WAS DEVELOPED & APPLIED TO ANALYSIS OF MULTIVITAMIN BLENDS.|4,4'-DIMETHOXY-DIQUINONE, REACTED QUANTITATIVELY WITH VITAMIN B1 THUS OFFERING A SIMPLE & RAPID METHOD FOR ITS DETERMINATION. ABSORPTION PEAK WAS @ 490 NM.

Thiamin status can be assessed by determining erythrocyte transketolase activity, by measuring the concentration of thiamin and its phosphorylated esters in blood or serum components using high-performance liquid chromatography, or by measuring urinary thiamin excretion under basal conditions or after thiamin loading.|The urinary excretion of thiamin is the indicator that has been used most widely in metabolic studies of thiamin requirements. ... Erythrocyte transketolase activity has also been widely used and is generally regarded as the best functional test of thiamin status, but it has some limitations for deriving the EAR and should be evaluated along with other indicators. In this test, erythrocytes are lysed and the transketolase activity is measured before and after stimulation by the addition of thiamin pyrophosphate (TPP); the basal level and the stimulated value (typically expressed as a multiple of the basal level, termed the activity coefficient or TPP effect) are measured. ... Factors other than thiamin status, such as genetic defects, may influence the enzyme activity and thus the test results.

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