fursultiamin and benphothiamine

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 AUC. 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).

Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Chemistry, Pharmaceutical; Cross-Over Studies; Fursultiamin; Humans; Male; Therapeutic Equivalency; Thiamine; Young Adult

In a multiple change-over study the bioequivalence of 3 thiamine preparations, used therapeutically as neurotropic agents for the treatment of polyneuropathies, was tested in a collective of 7 volunteers. After ingestion of a single dose of either 100 mg benfotiamin CS-benzoylthiamine-o-monophosphate), fursultiamin (thiamintetrahydrofurfuryldisulfide) or thiaminedisulfide, thiamine blood levels were analyzed for a 10-hour period. Thiamine was measured by HPLC after precolumn derivatization to thiochrome. The maximal thiamine concentration Cmax and its time (tmax) in plasma and hemolysate, the area under concentration time curve (AUC), and thiamine excretion in 24-hour urine were assessed as criteria of bioavailability. Additionally the erythrocytic transketolase activity (ETK) and alphaETK were determined as indicators of the cellular thiamine availability. After benfotiamin ingestion a more rapid and earlier increase of thiamine in plasma and hemolysate was observed in contrast to fursultiamin and the disulfide. All biokinetic data demonstrated a significantly improved thiamine bioavailability from benfotiamin compared with the other preparations. The lowest bioavailability was detected with thiamindisulfide. From our results it can be concluded that oral administration of benfotiamin is best suitable for therapeutical purposes owing to its excellent absorption characteristics.

Topics: Administration, Oral; Adult; Area Under Curve; Biological Availability; Fursultiamin; Half-Life; Humans; Middle Aged; Thiamine; Transketolase

Reduction of glucose metabolism in brain is one of the main features of Alzheimer's disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer's disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer's disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3alpha and -3beta, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer's disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer's disease treatment.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Brain; Cerebral Cortex; Cognition; Cognition Disorders; Dose-Response Relationship, Drug; Drug Administration Schedule; Fursultiamin; Glycogen Synthase Kinases; Isoenzymes; Maze Learning; Memory; Mice; Mice, Transgenic; Phosphorylation; Plaque, Amyloid; Presenilin-1; Swimming; tau Proteins; Thiamine