The percutaneous absorption of topically applied tretinoin and its effect on endogenous concentrations of tretinoin and its metabolites after single doses or long-term use.

Background: The percutaneous absorption of topically applied tretinoin cream and emollient cream formulations has not been comprehensively studied.

Objective: To assess tretinoin absorption and plasma levels of tretinoin and its metabolites after single and repeated topical tretinoin doses.

Methods: In study 1, 28 subjects were equally divided into four treatment groups that received a single dose of tritiated tretinoin in a 0.05% formulation of emollient cream (Renova, Retinova) or cream (Retin-A) alone or after 28 days of repeated nonradioactive doses. In study 2, subjects received single topical doses of tritiated tretinoin cream alone (n = 5) or after 1 year of nonradioactive applications (n = 4). Plasma, urine, and fecal samples were analyzed to determine absorption; plasma samples in study 1 were also analyzed for concentrations of tretinoin and its metabolites.

Results: Percutaneous absorption of tretinoin was approximately 2% after a single dose and after 28 days of daily application. In patients receiving long-term therapy (i.e., > 1 year), absorption averaged 1.1%. Mean plasma concentrations of tretinoin after 28 days of treatment with either tretinoin emollient cream or tretinoin cream were not significantly changed when compared with the corresponding endogenous concentrations before treatment.

Conclusion: Minimal percutaneous absorption of tretinoin was obtained after its topical application in cream formulations. Neither single-dose nor long-term treatment with topical tretinoin formulations appeared to affect the endogenous levels of tretinoin or its metabolites.