Systemic Absorption of Retinoic Acid

Abstract

The absorption of [I4C]retinoic acid (RA) from a commercial 0.05% cream formulation has been studied in the rhesus monkey and humans. The RA was applied to the shaved back of 6 animals for 24 hr at a dosage of 200 mg cream/100 cm² skin. Three animals had normal skin and three had dermatitic skin produced by 2 weeks' pretreatment of the back with 0.05% RA cream. RA 100 mg/50 cm² was also applied for 10 hr to the face of eight human subjects, four with normal skin and four with dermatitic skin secondary to 2 weeks' pretreatment with RA. In both sets of experiments, absorption was assessed from urinary excretion of radioactivity corrected for excretion via other routes.

The RA absorption in the monkey was found to be 9.6% and 48.3% of the dose, respectively, for normal and dermatitic skin. In humans the effect of dermatitic skin was much less, with absorption being 5.3% and 7.2% of the dose for normal and dermatitic skin, respectively. In dermatitic skin, the kinetics reflected a damaged barrier, with a peak rate of absorption being reached at approximately 5 hr. Once-daily application of RA cream to the face in humans results in a systemic load of 14 μg/day. Use of the monkey as a model is seen to have severe limitations.