Allegra Sarah, Puglisi Soraya, Borin Chiara, Chiara Francesco, Basile Vittoria, Calabrese Anna, Reimondo Giuseppe, De Francia Silvia
Laboratory of Clinical Pharmacology "Franco Ghezzo", Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, 10043 Turin, Italy.
Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, San Luigi Gonzaga Hospital, Orbassano, 10043 Turin, Italy.
Biomedicines. 2022 Aug 3;10(8):1873. doi: 10.3390/biomedicines10081873.
Background: A wide interindividual variability in mitotane concentrations and treatment-related dyslipidemia have been reported. Here, we aimed to underline the sex-related differences in the lipid profile in patients that underwent radical surgery of adrenocortical carcinoma during treatment with adjuvant mitotane. Methods: A chromatographic method was used to quantify the drug in plasma collected from adult patients with complete tumor resection, also considering active metabolite o,p’-DDE. Results: We observed different lipid profiles between males and females and between pre- and post-menopausal women. Considering the mitotane-related effects on lipid levels, we observed that higher drug concentrations were correlated with higher HDL in all the considered groups (p < 0.001), with total cholesterol both in males (p = 0.005) and females (p = 0.036), with triglycerides in postmenopausal females (p = 0.002) and with LDL in male patients (p < 0.001). Increases in o,p’-DDE were positively correlated with HDL levels in all the groups (p < 0.001) and negatively with LDL in all the groups (males p = 0.008, pre- and post-menopausal females p < 0.001), with total cholesterol in pre- (p = 0.016) and post-menopausal women (p = 0.01) and with triglycerides in premenopausal females (p = 0.005). Conclusions: This is the first study designed to evaluate sex differences in lipoprotein and lipid levels during mitotane adjuvant treatment; the results suggest that a gender and personalized approach could be useful to prevent and manage alterations in the lipid profile.
已有报道称米托坦浓度存在广泛的个体间差异以及与治疗相关的血脂异常。在此，我们旨在强调接受肾上腺皮质癌根治性手术并接受米托坦辅助治疗的患者血脂谱中的性别差异。方法：采用色谱法对成年肿瘤完全切除患者血浆中的药物进行定量分析，同时考虑活性代谢物邻，对'-滴滴伊。结果：我们观察到男性与女性之间以及绝经前和绝经后女性之间存在不同的血脂谱。考虑到米托坦对血脂水平的影响，我们观察到在所有考虑的组中，较高的药物浓度与较高的高密度脂蛋白相关（p < 0.001），与男性（p = 0.005）和女性（p = 0.036）的总胆固醇相关，与绝经后女性的甘油三酯相关（p = 0.002）以及与男性患者的低密度脂蛋白相关（p < 0.001）。邻，对'-滴滴伊的增加与所有组中的高密度脂蛋白水平呈正相关（p < 0.001），与所有组中的低密度脂蛋白呈负相关（男性p = 0.008，绝经前和绝经后女性p < 0.001），与绝经前（p = 0.016）和绝经后女性的总胆固醇相关（p = 0.01）以及与绝经前女性的甘油三酯相关（p = 0.005）。结论：这是第一项旨在评估米托坦辅助治疗期间脂蛋白和血脂水平性别差异的研究；结果表明，性别和个性化方法可能有助于预防和管理血脂谱的改变。
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