Grønhøj Larsen F, Steinkjer B, Jakobsen P, Hjorter A, Brockhoff P B, Nielsen-Kudsk F
Department of Dermatology, Bispebjerg Hospital, University of Copenhagen, Bispebjerg Bakke 23, 2400 Copenhagen NV, Denmark.
Br J Dermatol. 2000 Dec;143(6):1164-9. doi: 10.1046/j.1365-2133.2000.03883.x.
Acitretin has replaced etretinate in the treatment of various disorders of keratinization due to a considerably shorter terminal half-life. Possible esterification of acitretin to etretinate in the presence of ethanol has been reported.
To determine the plasma concentrations of etretinate as a metabolite in patients with various disorders of keratinization after multiple acitretin dosing, and to assess the influence of alcohol consumption using a questionnaire. In addition, to study the influence of alcohol consumption on the risk of metabolic formation of etretinate.
PATIENTS/METHODS: Eighty-six acitretin (Neotigason(R), Roche)-treated outpatients from three centres provided pre-dose (trough) samples for determining plasma concentrations of acitretin and its metabolites 13-cis-acitretin and etretinate. Patients received acitretin doses of between 0.1 and 1.3 mg kg-1 daily. The concentrations of etretinate, acitretin and 13-cis-acitretin were determined by reverse-phase high-performance liquid chromatography.
Of the 86 patients, 30 had detectable plasma etretinate levels. No etretinate was found in 20 patients who reported that they never drank alcohol, while etretinate was found in all 16 patients with an average weekly alcohol consumption of > 200 g ethanol, corresponding to about 15 U (1 U equals half a pint of standard beer or a wine glass of non-fortified wine). Etretinate was detected in 14 of 50 patients with a moderate weekly alcohol intake of up to 200 g ethanol. A trend linking higher alcohol intake with both higher risk of etretinate formation and higher etretinate levels was observed. The study also revealed that the ethylesterification only relates to acitretin (13-trans-) and not to the main metabolite 13-cis-acitretin, although the latter compound showed higher plasma trough concentration levels at steady state.
Owing to the teratogenic potential and possible side-effects of oral retinoids, fertile women especially should be informed about the importance of strict alcohol abstinence during treatment and for at least 2 months after stopping therapy. In case of non-compliance with alcohol abstinence a post-therapy contraceptive period of 2-3 years should be recommended.
由于阿维A的终末半衰期明显更短，其已取代依曲替酯用于治疗各种角化异常疾病。据报道，在乙醇存在的情况下，阿维A可能会酯化为依曲替酯。
测定多次服用阿维A后，各种角化异常疾病患者血浆中作为代谢产物的依曲替酯浓度，并通过问卷调查评估饮酒的影响。此外，研究饮酒对依曲替酯代谢形成风险的影响。
患者/方法：来自三个中心的86名接受阿维A（商品名Neotigason(R)，罗氏公司生产）治疗的门诊患者提供给药前（谷值）样本，用于测定血浆中阿维A及其代谢产物13 - 顺式阿维A和依曲替酯的浓度。患者每日接受的阿维A剂量为0.1至1.3 mg/kg。依曲替酯、阿维A和13 - 顺式阿维A的浓度通过反相高效液相色谱法测定。
86名患者中，30名患者的血浆依曲替酯水平可检测到。在报告从不饮酒的20名患者中未发现依曲替酯，而在平均每周饮酒量>200 g乙醇（约相当于15个单位，1个单位等于半品脱标准啤酒或一杯非强化葡萄酒）的所有16名患者中均发现了依曲替酯。在每周饮酒量适度高达200 g乙醇的50名患者中，有14名检测到依曲替酯。观察到饮酒量增加与依曲替酯形成风险增加及依曲替酯水平升高之间存在关联。该研究还表明，乙酯化仅与阿维A（13 - 反式）有关，而与主要代谢产物13 - 顺式阿维A无关，尽管后者在稳态时血浆谷值浓度水平更高。
由于口服维甲酸类药物具有致畸潜力和可能的副作用，尤其应告知育龄妇女在治疗期间及停药后至少2个月严格戒酒的重要性。如果不遵守戒酒规定，建议治疗后避孕2至3年。
