pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects药物动力学的健康受试者口服大剂量盐酸硫胺素.pdfVIP

Smithline et al. BMC Clinical Pharmacology 2012, 12:4 /1472-6904/12/4 RESEARCH ARTICLE Open Access Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects Howard A Smithline1,4*, Michael Donnino2 and David J Greenblatt3 Abstract Background: High 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. Methods: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated. Results: 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. Conclusion: 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. Trial Registration: ClinicalT: NC Background Thiamine is used to treat various genetic disorders Thiamine, vitamin B , was isolated in 1926 and synthe- linked to the above metabolic pathways and thiamine 1 sized in 1936. Its importance for preventing illness was deficiency syndromes (beriberi and Wernicke-Korsakoff known as early as the turn of the century. Thiamine syndrome). Oral thiamine may also have a role in treat- requirements are related to energy metabolism; specifi- ing some of the pathophysiologic conditions associated cally, 0.33 mg of thiamine are required for every 4400 kJ