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 a, beta, or t1/2 beta 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 C(max) for RRR (4.8 mug/mL) significantly greater than for all rac (4.0 mug/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.