Oral isotretinoin (13-cis-retinoic acid) therapy in severe acne: drug and vitamin A concentrations in serum and skin.
The disposition of oral isotretinoin to the skin and the effects of the drug on the vitamin A levels in serum and skin were studied in 17 patients with nodulocystic acne. All patients received 0.5 mg/kg/day for 3 months and 8 patients continued treatment with 0.75 mg/kg/day for another 3 months. The parent drug, the major metabolite (4-oxo-isotretinoin), and 2 natural retinoids (retinol and dehydroretinol) were monitored in serum and biopsies of uninvolved skin, using adsorption high-pressure liquid chromatography. During the initial 3 months of treatment the mean isotretinoin level in the serum was 145 ng/ml and in the epidermis 73 ng/g. The corresponding values for 4-oxo-isotretinoin were 615 and 113 ng/g, respectively. Even at the highest dosage there was no progressive accumulation of isotretinoin in serum, epidermis, or subcutis. After discontinuation of therapy the drug disappeared from both serum and skin within 2-4 weeks. The serum transport of vitamin A, monitored by the concentrations of retinol, retinol-binding protein, and prealbumin (transthyretin), was not affected by the treatment. By contrast, the retinol level in the epidermis increased by an average of 53% (p less than 0.01) and the dehydroretinol level decreased by 79% (p less than 0.001) as a result of 3 months of treatment. Both changes were reversible. The results suggest that isotretinoin therapy interferes with the endogenous vitamin A metabolism in the skin.
D000152:Acne Vulgaris / Q000097:blood / Q000188:drug therapy*; D000328:Adult; D001693:Biological Transport, Active / Q000187:drug effects; D002986:Clinical Trials as Topic; D005260:Female; D006801:Humans; D007536:Isomerism; D015474:Isotretinoin; D008297:Male; D012867:Skin / Q000032:analysis*; D014212:Tretinoin / Q000097:blood / Q000627:therapeutic use*; D014801:Vitamin A / Q000097:blood*
D014801:Vitamin A; D014212:Tretinoin; D015474:Isotretinoin