Clinical studies have shown that topical tretinoin is a potent drug and local reactions may occur. However, the risk of systemic toxicity is low be cause tretinoin has limited absorption through the skin, the retinoid remaining mostly on the stratum corneum.

It has been shown thal there is minimal systemic absorption of radiola belled tretinoin, even following pretreatment with topical tretinoin for 28 days, or as long as 1 year. Based on the measurement of radiolabel in plasma, Íaeces and urine, the total percutaneous absorption of tretinoin was approximately 2%. In view of the low percutaneous absorption and an average application of only 250mg 0.05% tretinoin cream (a dose of 2.5ug/kg for a 50 kg subject), this dose would not be sufficient to raise the normal endogenons plasma concentrations of tretinoin, which are in the range 2-5 mg/ml.

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