Alteration of thiamine pharmacokinetics by end-stage renal disease (ESRD)

Objective: In a comparative study with 20 end-stage renal disease (ESRD) pa tients the pharmacokinetics of two therapeutically used thiamine (vitamin B -1) preparations were assessed. Subjects, material and methods: After a sin gle oral dose of either 100 mg benfotiamin (S-benzoylthiamine-o-monophospha te, BTMP) or 100 mg thiamine mononitrate (TN), blood levels of thiamine pho sphate esters were analyzed by HPLC after precolumn derivatization to thioc hrome phosphate esters for a 24-hour period. Results: The pharmacokinetic p arameters AU(C0-24h), C-max and t(max) of the benfotiamin group in whole bl ood 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 BTMP group and T N 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 BTMP as well as TN. The activation co efficient (ETK-AC) decreased significantly from 1.10 to 1.04 vs. 1.12 to 1. 07 in both the BTMP as well as TN groups, respectively. In addition, a high transfer rate to thiamine diphosphate (TDP) was observed in the patients a fter ingestion of BTMP. The TDP concentration in whole blood increased by 2 .6 and 1.4 times from baseline levels to C-max in the BTMP and TN groups, r espectively. The AUC(0-24h) of TDP in whole blood after BTMP ingestion exce eded those after TN ingestion by 420%. Conclusion: These findings justify t he therapeutic application of BTMP in ESRD, because a high intracellular co ncentration of TDP may protect against numerous adverse effects of uremia i n the long run.