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


METHODS
After a single oral dose of either 100 mg benfotiamin (S-benzoylthiamine-o-monophosphate, BTMP) 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 benfotiamin 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 BTMP 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 BTMP 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 BTMP as well as TN groups, respectively. In addition, a high transfer rate to thiamine diphosphate (TDP) was observed in the patients after ingestion of BTMP. The TDP concentration in whole blood increased by 2.6 and 1.4 times from baseline levels to Cmax in the BTMP and TN groups, respectively. The AUC0-24h of TDP in whole blood after BTMP ingestion exceeded those after TN ingestion by 420%.


CONCLUSIONS
These findings justify the therapeutic application of BTMP in ESRD, because a high intracellular concentration of TDP may protect against numerous adverse effects of uremia in the long run.
Frank
T
T
Department of Human Nutrition, Institute of Nutrition, Friedrich Schiller University of Jena, Germany.
Bitsch
R
R
Maiwald
J
J
Stein
G
G
D002851:Chromatography, High Pressure Liquid; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013831:Thiamine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000493:pharmacokinetics*; D013833:Thiamine Monophosphate / Q000097:blood*
D013833:Thiamine Monophosphate; D013831:Thiamine; C013835:benphothiamine