Pharmacokinetics of high-dose oral thiamine hydrochloride in healthy subjects

Howard A Smithline, Michael Donnino, David J Greenblatt, Howard A Smithline, Michael Donnino, David J Greenblatt

Abstract

Background: High dose oral thiamine may have a role in treating diabetes, heart failure, and hypermetabolic states. The purpose of this study was to determine the pharmacokinetic profile of oral thiamine hydrochloride at 100 mg, 500 mg and 1500 mg doses in healthy subjects.

Methods: This was a randomized, double-blind, single-dose, 4-way crossover study. Pharmacokinetic measures were calculated.

Results: The AUC₀₋₁₀ hr and C(max) values increased nonlinearly between 100 mg and 1500 mg. The slope of the AUC₀₋₁₀ hr vs dose, as well as the C(max) vs dose, plots are steepest at the lowest thiamine doses.

Conclusion: Our study demonstrates that high blood levels of thiamine can be achieved rapidly with oral thiamine hydrochloride. Thiamine is absorbed by both an active and nonsaturable passive process.

Trial registration: ClinicalTrials.gov: NCT00981877.

Figures

Figure 1
Figure 1
Oral Thiamine Whole Blood Concentration vs Time Plot. The concentration of thiamine in plasma from 0 hour to 10 hours after 100 mg (♦), 500 mg (●) and 1500 mg (■) of oral thiamine. Error bars are standard deviations.
Figure 2
Figure 2
Oral Thiamine Plasma Concentration vs Time Plot. The concentration of thiamine in whole blood from 0 hour to 10 hours after 100 mg (♦), 500 mg (●) and 1500 mg (■) of oral thiamine. Error bars are standard deviations.
Figure 3
Figure 3
Semi-log Plot of the Terminal Phase of Oral Thiamine Whole Blood Concentration vs Time. The concentration of thiamine in whole blood from 4 hour to 10 hours after 100 mg (♦), 500 mg (●) and 1500 mg (■) of oral thiamine.
Figure 4
Figure 4
Semi-log Plot of the Terminal Phase of Oral Thiamine Plasma Concentration vs Time. The concentration of thiamine in plasma from 4 hour to 10 hours after 100 mg (♦), 500 mg (●) and 1500 mg (■) of oral thiamine.
Figure 5
Figure 5
Whole Blood 0 to 10 Hour AUC vs Thiamine Dose Plot. The mean area under the curve values for whole blood thiamine measures from time 0 hour to time 10 hours vs thiamine dose after 0 mg, 100 mg, 500 mg and 1500 mg of oral thiamine. Error bars are 95% confidence intervals.
Figure 6
Figure 6
Plasma 0 to 10 Hour AUC vs Thiamine Dose Plot. The mean area under the curve values for plasma thiamine measures from time 0 hour to time 10 hours vs thiamine dose after 0 mg, 100 mg, 500 mg and 1500 mg of oral thiamine. Error bars are 95% confidence intervals.
Figure 7
Figure 7
Whole Blood Cmax vs Thiamine Dose Plot. The mean maximum whole blood thiamine concentration between time 0 hour and time 10 hours vs thiamine dose after 0 mg, 100 mg, 500 mg and 1500 mg of oral thiamine. Error bars are 95% confidence intervals.
Figure 8
Figure 8
Plasma Cmax vs Thiamine Dose Plot. The mean maximum whole blood thiamine concentration between time 0 hour and time 10 hours vs thiamine dose after 0 mg, 100 mg, 500 mg and 1500 mg of oral thiamine. Error bars are 95% confidence intervals.

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