Rollman O, Vahlquist A
J Invest Dermatol. 1986 Apr;86(4):384-9. doi: 10.1111/1523-1747.ep12285651.
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.
对17例结节囊肿性痤疮患者研究了口服异维A酸在皮肤中的分布以及该药物对血清和皮肤中维生素A水平的影响。所有患者均接受0.5mg/kg/天的剂量治疗3个月，8例患者继续以0.75mg/kg/天的剂量治疗另外3个月。采用吸附高压液相色谱法监测血清和未受累皮肤活检组织中的母体药物、主要代谢产物（4-氧代异维A酸）以及2种天然类维生素A（视黄醇和脱氢视黄醇）。在治疗的最初3个月期间，血清中异维A酸的平均水平为145ng/ml，表皮中为73ng/g。4-氧代异维A酸的相应值分别为615和113ng/g。即使在最高剂量下，血清、表皮或皮下组织中异维A酸也没有进行性蓄积。停药后，药物在2-4周内从血清和皮肤中消失。通过视黄醇、视黄醇结合蛋白和前白蛋白（转甲状腺素蛋白）的浓度监测的维生素A的血清转运不受治疗影响。相比之下，经过3个月的治疗，表皮中的视黄醇水平平均升高了53%（p<0.01），脱氢视黄醇水平降低了79%（p<0.001）。这两种变化都是可逆的。结果表明，异维A酸治疗会干扰皮肤中内源性维生素A的代谢。
