Thiamine hydrochloride

Endpoint summary

Description of key information

Published Information:

Thiamine is well absorbed from the gastro-intestinal tract following oral administration, although the absorption of large doses is limited. It is also rapidly absorbed following intramuscular administration. It is widely distributed to most body tissues, and appears in breast milk. Thiamine is not stored to any appreciable extent in the body and amounts in excess of the body’s requirements are excreted in the urine as unchanged thiamine or as metabolites[1-3].

Following oral ingestion, thiamine is well absorbed in the proximal intestinal tract. The efficiency of thiamine absorption is reduced upon consumption of thiamine above 5 mg/day[3-5]. At physiologic concentrations, thiamine is transported primarily by an active process, whereas at higher concentrations thiamine uptake is predominantly a passive process[6-8].

In a kinetic study using pharmacological doses of vitamin B1, the intramuscular and oral route were compared. Doses of 250 mg p.o. every 12 hours versus 500 mg i.m. once a day for 11 days resulted in a steady state plasma vitamin B1 concentration after 7 and 5.6 days, respectively. The mean elimination half-life value was calculated to be approximately 1.8 days[9].

Free thiamine functions as the precursor for thiamine diphosphate (TDP, also called thiamine pyrophosphate TPP), which acts as a coenzyme for enzymes involved in carbohydrate and branched-chain amino acid metabolism, and in energy-yielding reactions. In blood and tissues, thiamine is present as the free form and mono-, di- and tri-phosphorylated forms, which are interconvertible. Thiamine phosphorylation takes place in most cells/tissues, but mainly in the liver. Thiamine is transported into mammalian cells by specific transporters and immediately phosphorylated to its diphosphate form by cytosolic pyrophosphokinase[10, 11].

In blood, thiamine is mainly found in erythrocytes (> 80% of total thiamine) in the form of TDP and some TTP (thiamine triphosphate), while low amounts of the vitamin are present in plasma, as free thiamine, TMP (thiamine monophosphate) and protein-bound TDP[12]. In human tissues, thiamine occurs mostly in phosphorylated forms as TMP, TDP, TTP, as well as its non-phosphorylated form (‘free thiamine’). Adenosine thiamine triphosphate (ATTP) is also found in some tissues.

Thiamine is widely distributed to most body tissues, but there is no appreciable storage in any tissue, and a regular thiamine intake is necessary. The total thiamine content of the adult human has been estimated to be about 25–30 mg, located mostly in the skeletal muscles, heart, brain, liver and kidneys, and the biological half-life of the vitamin is probably in the range of 9 to 18 days[13, 10].

Free thiamine, TPP, and TMP in excess of tissue needs are eliminated mainly via urinary excretion either unchanged or as several (about 20) metabolites[13]. After an oral dose of thiamine, peak excretion occurs in about 2 hours, and excretion is nearly complete after 4 hours[14, 15], confirming earlier reports from the 1940s of prompt urinary excretion of thiamine. The level of unchanged thiamine in the urine increases as intake increases.

 

(No information on absorption/exposure to thiamine via the inhalation or dermal route was found.)

References

1   Martindale The Extra Pharmacopoeia; 32nd ed.Pharmaceutical Press; page 1361, 1999

2   Weber W, Nitz M, Looby M (1990) Nonlinear kinetics of the thiamine cation in humans: saturation of nonrenal clearance and tubular reabsorption.J Pharmacokinet Biopharm18(6):501-523.

3   Tallaksen CM, Sande A, Bohmer T, Bell H, Karlsen J (1993) Kinetics of thiamin and thiamin phosphate esters in human blood, plasma and urine after 50 mg intravenously or orally.Eur J Clin Pharmacol44(1):73-78.

4   Friedemann TE, Kmieciak TC, et al.(1948) The absorption, destruction, and excretion of orally administered thiamin by human subjects.Gastroenterology11(1):100-114.

5   Davis RE, Icke GC, Thom J, Riley WJ (1984) Intestinal absorption of thiamin in man compared with folate and pyridoxal and its subsequent urinary excretion.J Nutr Sci Vitaminol (Tokyo)30(5):475-482.

6   Thomson AD and Leevy CM (1972) Observations on the mechanism of thiamine hydrochloride absorption in man.Clin Sci43(2):153-163.

7   Hoyumpa AM, Jr. (1982) Characterization of normal intestinal thiamin transport in animals and man.Ann N Y Acad Sci378:337-343.

8   Smithline HA, Donnino M, Greenblatt DJ (2012) Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects.BMC Clin Pharmacol124.

9   Royer-Morrot MJ, Zhiri A, Paille F, Royer RJ (1992) Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men.Eur J Clin Pharmacol42(2):219-222.

10 Manzetti S, Zhang J, van der Spoel D (2014) Thiamin function, metabolism, uptake, and transport.Biochemistry53(5):821-835.

11  Bettendorff L and Wins P (2013) Biological functions of thiamine derivatives: focus on non-coenzyme roles.OA Biochemistry1(1):10. http://www.oapublishinglondon.com/article/860#

12 Gangolf M, Czerniecki J, Radermecker M, Detry O, Nisolle M, Jouan C, Martin D, Chantraine F, Lakaye B, Wins P, Grisar T, Bettendorff L (2010) Thiamine status in humans and content of phosphorylated thiamine derivatives in biopsies and cultured cells.PLoS One5(10):e13616.

13 Ariaey-Nejad MR, Balaghi M, Baker EM, Sauberlich HE (1970) Thiamin metabolism in man.Am J Clin Nutr23(6):764-778.

14 Levy G and Hewitt RR (1971) Evidence in man for different specialized intestinal transport mechanisms for riboflavin and thiamin.Am J Clin Nutr24(4):401-404.

15 Morrison AB and Campbell JA (1960) Vitamin absorption studies. I. Factors influencing the excretion of oral test doses of thiamine and riboflavin by human subjects.J Nutr72435-440.