Pharmacokinetics and Bioavailability of the RRR and All Racemic Stereoisomers of Alpha-Tocopherol in Humans After Single Oral Administration

The plasma and red blood cell pharmacokinetics and bioavailability of the natural source (RRR, d) and all racemic (all rac, dl) stereoisomers of alpha‐tocopherol were studied in 12 men in a double‐blind randomized crossover study. Subjects were administered two 400‐mg soft‐gelatin capsules of either RRR or all rac alpha‐tocopherol. Plasma alpha‐tocopherol concentrations were determined by high‐performance liquid chromatography at various time intervals for up to 96 hours postadministration. Pharmacokinetic modeling of the data showed that alpha‐tocopherol was absorbed after a 2 to 4 hour lagtime and maximum plasma concentration occurred from 12 to 14 hours postadministration. There were no significant differences in the Ka, t1/2 α, β, or t1/2 β between RRR and all rac. Mean plasma alpha‐tocopherol concentrations were greater for RRR than all rac from 10 to 96 hours postadministration and significantly greater at 24 hours (P < .05). The red blood cell alpha‐tocopherol concentration from the RRR preparation was significantly greater than from the all rac preparation from 24 to 96 hours postadministration with Cmax for RRR (4.8 μg/mL) significantly greater than for all rac (4.0 μg/mL, P < .05). The RRR AUC0–96 for both plasma and red blood cells were significantly greater than the all rac AUC0–96 (P < .05) indicating a greater bioavailability of RRR versus all rac alpha‐tocopherol. This difference in overall bioavailability was apparently not due to a single pharmacokinetic component.