Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated.The AUC0-10 hr and Cmax values increased nonlinearly between100 mg and 1500 mg. The slope of the AUC0-10 hr vs dose, as well as the Cmax vs dose, plots are steepest at the lowest thiamine doses.Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process.ClinicalTrials.gov: NCT00981877Thiamine, vitamin B1, was isolated in 1926 and synthesized in 1936. Its importance for preventing illness was known as early as the turn of the century. Thiamine requirements are related to energy metabolism; specifically, 0.33 mg of thiamine are required for every 4400 kJ of energy. For adults the DRI of thiamine is between 1.1 and 1.4 mg per day. The primary active form of the vitamin, thiamine diphosphate (ThDP), is also known as thiamine pyrophosphate (TPP). ThDP is a necessary cofactor for enzymes related to carbohydrate metabolism: pyruvate dehydrogenase (PDH), α-ketoglutarate dehydrogenase, and transketolase.Thiamine, vitamin B1, is not synthesized by humans and is not stored in large quantities in humans [1]. One of its phosphorylated forms, thiamine diphosphate, also known as thiamine pyrophosphate, is the primary active form of the vitamin. Thiamine diphosphate is a necessary co-factor for several enzymes involved in the glycolytic pathway, citric acid cycle, pentose phosphate pathway, and degradation of branched chain amino acids.Thiamine is used to treat various genetic disorders linked to the above metabolic pathways and thiamine deficiency syndromes (beriberi and Wernicke-Korsakoff syndrome). Oral thiamine may also have a role in treating some of the pathophysiologic conditions associated with diabetes, heart failure, and hypermetabolic states [2-5].The optimum dosing for these beneficial effects is unknown. Rare side effects of thiami