Kinetics of permeation and metabolism of alpha-tocopherol and alpha-tocopheryl acetate in micro-Yucatan pig sin.

The objective of this research was to investigate the permeation and metabolism of alpha-tocopheryl acetate (alpha-TAc) and alpha-tocopherol (alpha-T) from solution and emulsion formulations and to delineate the kinetics of such metabolism. Simple formulations containing alpha-TAc and alpha-T were applied to fresh, viable micro-Yucatan skin dermatomed to a thickness of 250-300 microns, as a finite dose in a flow-through diffusion system. The experiments were stopped at time intervals of 2, 6, 12, and 24 hours. At the end of each time interval, the amounts removed by washing, retained in the stratum corneum (SC), and penetrated into the viable skin and receptor were determined by a validated HPLC method. Receptor concentrations were below the limit of detection. alpha-TAc underwent metabolism in pig skin to the active antioxidant alpha-T. The metabolite appeared as early as two hours after application. The extent of metabolism was highest at 6-12 hours after application. No metabolism was detected in the stratum corneum. Delivery of alpha-T from isopropyl myristate (IPM) solution was more efficient than utilization of alpha-TAc from the same solution. Approximately 1.5% of alpha-T yielded the same viable skin concentration as 5% alpha-TAc. Topical application of alpha-tocopherol or its prodrug acetate was capable of enhancing the overall antioxidant capacity of pig skin. The hydrolytic pathway of alpha-TAc leading to the active antioxidant alpha-T could possibly be saturable.