title: Comparative Pharmacokinetic Analysis of Thiamine and Its Phosphorylated Metabolites Administered as Multivitamin Preparations.
abstract: Fursultiamine and benfotiamine are lipophilic 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.
  
  
  
  Two randomized, single-dose, 2-way crossover, full PK studies were conducted in healthy Korean male subjects (n = 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 reference 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.
  
  
  
  The systemic thiamine exposure of the test compound was slightly greater than that of reference A, based on the geometric mean ratio (%) of the AUClastvalue for plasma (116.6%) and hemolysate (137.5%). The thiamine diphosphate (TDP) distribution between plasma and hemolysate showed clear differences according to the formulations, in that more TDP was present in the hemolysate when thiamine was given as the test formulation. The AUClastvalue of plasma thiamine showed a >300% increase when thiamine was given as the test formulation in study B. The summed total exposure to thiamine (thiamine + 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.
  
  
  
  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).
authors.affiliation: Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Wan-Su
authors.initials: WS
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Jongtae
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Taegon
authors.initials: T
authors.lastname: Hong
authors.affiliation: Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Gabjin
authors.initials: G
authors.lastname: Park
authors.affiliation: Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Sunil
authors.initials: S
authors.lastname: Youn
authors.affiliation: Biosuntek Laboratory Co. Ltd., Sungnam, Republic of Korea.
authors.forename: Youngwhan
authors.initials: Y
authors.lastname: Seo
authors.affiliation: Biosuntek Laboratory Co. Ltd., Sungnam, Republic of Korea.
authors.forename: Sanghun
authors.initials: S
authors.lastname: Lee
authors.affiliation: Department of Pharmacology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address: waystolove@catholic.ac.kr.
authors.forename: Seunghoon
authors.initials: S
authors.lastname: Han
mesh_terms: D000284:Administration, Oral; D000328:Adult; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D018592:Cross-Over Studies; D005666:Fursultiamin / Q000493:pharmacokinetics*; D006801:Humans; D008297:Male; D013810:Therapeutic Equivalency; D013831:Thiamine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D055815:Young Adult
chemical_list: D005666:Fursultiamin; D013831:Thiamine; C013835:benphothiamine
keywords: multivitamin; pharmacokinetics; phosphorylated; thiamine