Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

Abstract

BackgroundHigh dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects.MethodsThis was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated.ResultsThe 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.ConclusionOur 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.Trial RegistrationClinicalTrials.gov: NCT00981877

Chemical and genetic validation of thiamine utilization as an antimalarial drug target

“…It is worth noting that the high dose of oral oxythiamine required in this and previous studies may be due to a concomitant low plasma concentrations of oxythiamine, as has been previously shown to be the case for orally administered thiamine in humans 26 . Therefore, although oxythiamine is unlikely to be developed as an antimalarial in its own right, we propose that it can serve as a starting point from which to design antimalarials targeting this pathway.…”

Thiamine Therapy for Heart Failure: a Promise or Fiction?

“…Those who exhibit low thiamine levels may be given thiamine supplementation. High oral doses often result in high blood concentrations [23]. Thiamine is a relatively safe drug and no major side effects have been reported at high doses in the range of 300-900-mg daily dose.…”

Pharmacokinetics of the transdermal delivery of benfotiamine

“…The systemic circulating level of thiamine following oral administration of thiamine is carefully regulated by metabolism and excretion mechanisms, and as a result, the circulating concentrations do not correspond to the oral dose [22]. Thiamine supplementation does increase the blood concentrations of thiamine and its derivatives [23][24][25], and it even shows better reproducible benefit for diabetic nephropathy [26]. In experimental diabetes, benfotiamine increased plasma thiamine in the diabetic state with similar potency to that of dosing with thiamine itself [18,27].…”