Alteration of thiamine pharmacokinetics by end-stage renal disease (ESRD).
Frank T, Bitsch R, Maiwald J, Stein G.
Department of Human Nutrition
Institute of Nutrition
Friedrich Schiller University of Jena, Germany.
Int J Clin Pharmacol Ther. 1999 Sep;37(9):449-55.
Abstract
OBJECTIVE: In a comparative study with 20 end-stage renal disease (ESRD) patients the pharmacokinetics of two therapeutically used thiamine (vitamin B1) preparations were assessed.
SUBJECTS, MATERIAL AND METHODS: After a single oral dose of either 100 mg benfotiamine
or 100 mg thiamine mononitrate (TN), blood levels of thiamine phosphate esters were analyzed by HPLC after precolumn derivatization to thiochrome phosphate esters for a 24-hour period.
RESULTS: The pharmacokinetic parameters AUC0-24h, Cmax and tmax of the benfotiamine
group in whole blood and plasma exceeded significantly those in the TN group. Only 1.0 vs. 0.6% of the administered dose were excreted in urine in the
benfotiamine group and TN group, respectively. A high cellular efficacy, as was concluded from the short-term stimulation of the thiamine-dependent transketolase activity in erythrocytes (ETKA), was assessed for
benfotiamine as well as TN. The activation coefficient (ETK-AC) decreased significantly from 1.10 to 1.04 vs. 1.12 to 1.07 in both the
benfotiamine as well as TN groups, respectively. In addition, a high transfer rate to thiamine diphosphate (TDP) was observed in the patients after ingestion of
benfotiamine. The TDP concentration in whole blood increased by 2.6 and 1.4 times from baseline levels to Cmax in the
benfotiamine and TN groups, respectively. The AUC0-24h of TDP in whole blood after
benfotiamine ingestion exceeded those after TN ingestion by 420%.
CONCLUSION: These findings justify the therapeutic application of benfotiamine in end-stage renal disease, because a high intracellular concentration of TDP may protect against numerous adverse effects of uremia in the long run.
