Unit of Infectious Diseases, Department of Medical Sciences, Amedeo di Savoia Hospital, University of Turin, Turin, Italy.
Department of Biological and Clinical Sciences, S. Luigi Gonzaga Hospital, University of Turin, Orbassano, TO, Italy.
J Pharm Pharmacol. 2017 Nov;69(11):1524-1530. doi: 10.1111/jphp.12798. Epub 2017 Aug 15.
Mitotane is the reference drug for the adrenocortical carcinoma treatment; its pharmacological activity seems to depend on drug transformation in two active metabolites: o,p'-DDE (dichlorodiphenylethene) and o,p'-DDA (dichlorodiphenylacetate). Mitotane and metabolites are lipophilic agents; thus, they tend to accumulate into adipose tissues (white and brown), which change their prevalence seasonally. Aim of the work was to evaluate mitotane and metabolites plasma levels variation over the year, in adrenocortical cancer patients treated with Lysodren for at least 6 months.
We enrolled a group of 86 adrenocortical carcinoma diagnosed patients, who underwent radical surgery and started mitotane as adjuvant treatment. For drug and metabolites plasma level (from samples collected ~12 h after the dose administration of mitotane, just before the subsequent administration) determination, a validated chromatographic method was used.
Results showed an evidence of a seasonal trend for the three substance (o,p'-DDD, o,p'-DDE and o,p'-DDA) plasma levels, in terms of acrophases and lower values. Furthermore, it came out that male patients need a higher significant mitotane drug dose than female patients to reach mitotane therapeutic window.
In conclusion, this is the first study assessing a mitotane plasma level variation over the year, but further studies in larger cohorts are required.
米托坦是治疗肾上腺皮质癌的参考药物；其药理活性似乎取决于两种活性代谢物：邻，对-DDE（二氯二苯乙烯）和邻，对-DDA（二氯二苯乙酸）的药物转化。米托坦和代谢物是亲脂性药物；因此，它们倾向于积聚到脂肪组织（白色和棕色）中，其流行季节会发生变化。这项工作的目的是评估至少接受 Lysodren 治疗 6 个月的肾上腺皮质癌患者的米托坦和代谢物血浆水平随时间的变化。
我们招募了一组 86 名被诊断为肾上腺皮质癌的患者，他们接受了根治性手术，并开始接受米托坦作为辅助治疗。为了测定药物和代谢物的血浆水平（从米托坦给药后约 12 小时采集的样本中，即在随后的给药前），我们使用了一种经过验证的色谱方法。
结果表明，三种物质（邻，对-DDD、邻，对-DDE 和邻，对-DDA）的血浆水平存在季节性趋势的证据，表现为峰值和低值。此外，男性患者需要比女性患者更高的米托坦药物剂量才能达到米托坦的治疗窗。
总之，这是第一项评估米托坦血浆水平随时间变化的研究，但需要在更大的队列中进行进一步的研究。
