500 mg 4 times daily for 2 weeks

Evaluation of in vitro permeation and deposition of SMM (methylmethionine) through hairless mouse skin was carried out by using Keshary- Chien diffusion cells at 32°C, which have 1.77 cm2 of the surface area for diffusion. After sacrificing the hairless mice by cervical dislocation, the dorsal skin was cut to about 3 cm x 3 cm size and the subcutaneous fat was removed. Then, they were fixed between the donor and receptor cells, laying the stratum corneum toward the donor cells. The donor cells contained 2% (w/v) or 5% (w/v) SMM in the 50:50 (v/v) mixture (1.0 mL) of PG and double distilled water (DDW) with or without permeation enhancers, and were covered with parafilm to prevent evaporation. The receptor cells were filled with DDW (13.0 mL) and continuously stirred by magnetic bar. After applying SMM solution on the donor cells, 0.5 mL of the receptor solution was collected at 3, 6, 9, and 12 hr and added immediately with an equal volume of fresh media. SMM in the receptor solutions was analyzed using LC-MS/MS.