Sebum excretion rate in subjects treated with oral all-trans-retinoic acid

Background and Objective: It is generally accepted that the inhibition of sebum excretion has a predictive value for anti-acne activity, Whereas oral 13-cis-retinoic acid (13-cis-RA) decreases sebum excretion, it has not been shown so far if oral all-trans-retinoic acid (tretinoin, tRA) does so, The aim of this exploratory study was to investigate the effect of oral tRA on the sebum excretion rate (SER) in young male subjects. Methods: 12 healthy volunteers with a baseline SER above 1.0 mu g/cm(2)/min were treated with 20 mg/day tRA for 4 weeks, The SER was measured at weeks 2 and 4, Adverse reactions were recorded. Results: The mean SER varied from 1.56 at baseline to 1.65 at week 2 and to 1.49 mu g/cm(2)/min at week 4. Comparison with values obtained in the same subjects previously treated with either 13-cis-RA or 9-cis-retinoic acid indicated that tRA less sebosuppressive. Mucocutaneous reactions and headache were the most frequent side effects of oral tRA. Conclusion: The lack of effect on the SER suggests that oral tRA would probably be ineffective against acne, The fact that, of the three isomers tested, only 13-cis-RA (which does not bind to nuclear receptors) shows activity may suggest that sebosuppression is not nuclear receptor mediated. We discuss other hypotheses related to pharmacokinetics.