Clinical Therapeutics/Volume ], Number ], 2016 Comparative Pharmacokinetic Analysis of Thiamine and Its Phosphorylated Metabolites Administered as Multivitamin Preparations Wan-Su Park, MS 1 ; Jongtae Lee, MD, PhD 1 ; Taegon Hong, MD, PhD 1 ; Gabjin Park, MD 1 ; Sunil Youn, MD 1 ; Youngwhan Seo, PhD 2 ; Sanghun Lee, MS 2 ; and Seunghoon Han, MD, PhD 1 1 Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea; and 2 Biosuntek Laboratory Co. Ltd., Sungnam, Republic of Korea ABSTRACT Purpose: Fursultiamine and benfotiamine are lip- ophilic thiamine derivatives used as oral sources of thiamine. Although there are many publications on the pharmacokinetic (PK) properties of thiamine- containing products, no direct comparisons between these agents . We aimed to compare the PK profiles of these lipophilic thiamine derivatives and to compare the extent of the increase in bioavailability to that of naïve thiamine. Methods: Two randomized, single-dose, 2-way crossover, full PK studies were conducted in healthy Korean male subjects (n ¼ 24 per group). Among the test compounds, fursultiamine was compared with benfotiamine (reference A in study A) and thiamine nitrate (reference B in study B). All formulations were multivitamin preparations containing the test or refer- ence formulation as the major thiamine source. In study A, the plasma and hemolysate concentrations of thiamine and its metabolites were measured, while only the plasma thiamine concentration was assayed in study B. Findings: The systemic thiamine exposure of the test compound was slightly greater than that of reference A, based on the geometric mean ratio (%) of the AUC last value for plasma (116.6%) and hemolysate (137.5%). The thiamine diphosphate (TDP) distribution between plasma and hemolysate showed clear differences accord- ing to the formulations, in that more TDP was present in the hemolysate when thiamine was given as the test formulation. The AUC last value of plasma thiamine showed a 4300% increase when thiamine was given as the test formulation in study B. The summed total exposure to thiamine (thiamine þ TDP in both plasma and hemolysate) observed as a point estimate after the administration of fursultiamine was slightly greater than that with benfotiamine; however, the 90% CI was within the conventional bioequivalence range. Implications: These findings support clear benefits of lipophilic thiamine derivatives in the absorption of thiamine in healthy volunteers. Clinical Research Information Service identifiers: KCT0001419 (study A), KCT0001628 (study B). (Clin Ther. 2016;]:]]]– ]]]) & 2016 Elsevier HS Journals, Inc. All rights reserved. Key words: multivitamin, pharmacokinetics, phos- phorylated, thiamine. INTRODUCTION Thiamine, also known as vitamin B 1 , plays a fundamental role in energy metabolism. 1 It is not synthesized in the human body; thus, it needs to be ingested via the diet or as a nutritional supplement to maintain homeostasis. 2 Thiamine has several phosphorylated metabolites: thiamine monophosphate (TMP), thiamine diphosphate (TDP), and thiamine triphosphate. TDP is biologically active and acts as a cofactor for several enzymes, such as pyruvate dehydrogenase, α-ketoglutarate dehydrogenase, and transketolase, whereas it remains unknown as to whether there is a speci fic biological role for TMP in humans. 1, 3 The absorption of thiamine occurs primarily in the jujunum and ileum, with lesser amounts absorbed in the duodenum. Free thiamine is transported in the proximal Accepted for publication August 24, 2016. http://dx.doi.org/10.1016/j.clinthera.2016.08.009 0149-2918/$- see front matter & 2016 Elsevier HS Journals, Inc. All rights reserved. ] 2016 1