CONCENTRATION OF TEMAROTENE (RO-15-0778) AND ITS METABOLITE RO-14-6113 IN PLASMA AND SKIN OF HAIRLESS RAT

The aim of this preliminary report was to measure plasma and skin conc entrations of Ro 15-0778 and its phenolic metabolite Ro 14-6113 in hai rless rats receiving orally 10 mg/kg of Temarotene once daily during 1 0 days. Blood (2-3 ml) and skin (200-300 mg) samples were taken at dif ferent time points between 0.5 and 240 h after the last dose. We used a highly sensitive HPLC method for simultaneous determination of the t wo compounds with a quantification limit of 2 ng/ml in plasma and 10 n g/g in total skin (epidermis and dermis). After 10 h, plasma concentra tions of Ro 14-6113 were 5-13 times higher than for Ro 15-0778. Ro 14- 6113 concentrations in the skin were 4-10 times higher than for Ro 15- 0778 within the initial 48 h. The concentrations of both compounds in the skin were higher than concentrations in plasma.