T. Frank et al., High thiamine diphosphate concentrations in erythrocytes can be achieved in dialysis patients by oral administration of benfotiamine, EUR J CL PH, 56(3), 2000, pp. 251-257
Objective: The influence of either orally administered S-benzoylthiamine-O-
monophosphate (benfotiamine) or thiamine nitrate on the thiamine status was
tested in a randomised, two-group comparison study in 20 end-stage renal d
isease (ESRD) patients. Main outcome measures were the pharmacokinetics of
thiamine diphosphate (TDP) in blood, the in vitro erythrocyte transketolase
activity, its activation coefficient (alpha-ETK) and the TDP concentration
in erythrocytes.
Methods: After ingestion of a single dose of either 100 mg thiamine nitrate
(corresponding to 305 mu mol thiamine) or 100 mg benfotiamine (correspondi
ng to 214 mu mol thiamine), the blood levels of thiamine phosphate esters w
ere analysed by means of high-performance liquid chromatography for a 24-h
period. The TDP concentration in erythrocytes was calculated using the haem
atocrit and TDP concentration in blood. Erythrocyte transketolase activity
and alpha-ETK were measured before and 10 h after administration. The pharm
acokinetics of TDP in blood were compared with healthy subjects of other st
udies retrieved from database query.
Results: Regarding the blood concentrations of TDP, the patients with ESRD
had a 4.3 times higher area under the concentration-time curve after benfot
iamine administration than after thiamine nitrate. After benfotiamine admin
istration, the peak plasma concentration of TDP exceeded that in healthy su
bjects by 51%. In the ESRD patients, after 24 h, the mean TDP concentration
in erythrocytes increased from 158.7 +/- 30.9 ng/ml initially to 325.8 +/-
50.9 ng/ml after administration of benfotiamine and from 166.2 +/- 51.9 ng
/ml to 200.5 +/- 50.0 ng/ml after thiamine nitrate administration. The rati
o between the maximum erythrocyte TDP concentration and basal concentration
was 2.66 +/- 0.6 in the benfotiamine group and 1.44 +/- 0.2 in the group r
eceiving thiamine nitrate (P < 0.001). After 24 h, it was 2.11 +/- 0.4 and
1.23 +/- 0.2, respectively. The transketolase activity increased from 3.54
+/- 0.7 mu kat/l initially to 3.84 +/- 0.6 mu kat/l after benfotiamine inta
ke (P = 0.02) and from 3.71 +/- 0.8 mu kat/l to 4.02 +/- 0.7 mu kat/l after
thiamine nitrate intake (P = 0.08). Likewise, alpha-ETK decreased from ini
tially 1.10 +/- 0.07 to 1.04 +/- 0.04 (P = 0.04) and from 1.12 +/- 0.05 to
1.08 +/- 0.06 (P = 0.09). After 24 h, the phosphorylation ratio in whole bl
ood decreased from 12.9 +/- 6.9 initially to 5.6 +/- 3.2 after benfotiamine
administration (P = 0.02) and from 13.5 +/- 7.3 to 9.0 +/- 4.8 (P = 0.03)
after administration of thiamine nitrate. No correlation between erythrocyt
e TDP concentration and transketolase activity and/or alpha-ETK was observe
d in ESRD patients, either before or 10 h after administration.
Conclusion: Compared with thiamine nitrate, the oral administration of benf
otiamine leads to higher TDP concentrations in erythrocytes accompanied wit
h a significant improvement of the erythrocyte transketolase activity in ES
RD patients.