Bershad S, Rubinstein A, Paterniti J R, Le N A, Poliak S C, Heller B, Ginsberg H N, Fleischmajer R, Brown W V
N Engl J Med. 1985 Oct 17;313(16):981-5. doi: 10.1056/NEJM198510173131604.
Abnormalities in plasma lipids are a recognized side effect of isotretinoin therapy for nodulocystic acne. We studied 60 patients during 20 weeks of isotretinoin therapy, to measure changes in plasma lipids and lipoproteins, to compare plasma lipid responses in men and women, and to determine whether there are alterations in levels of lipoprotein lipase or hepatic triglyceride lipase that could explain the development of isotretinoin-induced hypertriglyceridemia. Mean triglyceride levels rose in men and women, with maximum mean increases of 46.3 mg per deciliter (P less than 0.0001) and 52.3 mg per deciliter (P less than 0.002), respectively. The maximum level was reached by 4 weeks of therapy in men but not until the 12th week in women. Nine of 53 patients (17 per cent) completing 20 weeks of isotretinoin therapy acquired hypertriglyceridemia, with values of 200 to 600 mg per deciliter. Both men and women had significant increases in mean plasma levels of cholesterol and low-density-lipoprotein cholesterol and decreases in mean levels of high-density-lipoprotein cholesterol. There were no significant changes in mean levels of lipoprotein lipase or hepatic triglyceride lipase. Plasma lipid and lipoprotein levels returned to base line by eight weeks after discontinuation of the drug. If sustained over a long period, the change in the ratio of low-density-lipoprotein cholesterol to high-density-lipoprotein cholesterol that we observed, from 2.4 to 3.0 (P less than 0.0001), would predict an increased risk of cardiovascular disease.
血浆脂质异常是异维甲酸治疗结节囊肿性痤疮公认的副作用。我们对60例患者进行了为期20周的异维甲酸治疗研究，以测量血浆脂质和脂蛋白的变化，比较男性和女性的血浆脂质反应，并确定脂蛋白脂肪酶或肝甘油三酯脂肪酶水平是否存在变化，这些变化可以解释异维甲酸诱导的高甘油三酯血症的发生。男性和女性的平均甘油三酯水平均升高，平均最大增幅分别为每分升46.3毫克（P<0.0001）和每分升52.3毫克（P<0.002）。男性在治疗4周时达到最高水平，而女性直到第12周才达到。53例完成20周异维甲酸治疗的患者中有9例（17%）出现高甘油三酯血症，值为每分升200至600毫克。男性和女性的血浆胆固醇和低密度脂蛋白胆固醇平均水平均显著升高，高密度脂蛋白胆固醇平均水平降低。脂蛋白脂肪酶或肝甘油三酯脂肪酶的平均水平没有显著变化。停药8周后，血浆脂质和脂蛋白水平恢复到基线。如果我们观察到的低密度脂蛋白胆固醇与高密度脂蛋白胆固醇的比值变化（从2.4增至3.0，P<0.0001）长期持续下去，预计心血管疾病风险会增加。
