Allegra Sarah, Puglisi Soraya, Brescia Irene, 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, S. Luigi Gonzaga Hospital, 10043 Orbassano, TO, Italy.
Internal Medicine, Department of Clinical and Biological Sciences, University of Turin, S. Luigi Gonzaga Hospital, 10043 Orbassano, TO, Italy.
Life (Basel). 2021 Mar 23;11(3):266. doi: 10.3390/life11030266.
(1) Background: In clinical settings, data regarding sex are rarely investigated. In women, factors such as body size and composition, hormonal variations, metabolism, and access to care systems and therapy could strongly influence the pharmacological management and the outcome of the therapy. To underline this sex-related difference, we retrospectively collected data from adrenocortical carcinoma patients treated with mitotane, and then evaluated sex-related pharmacokinetics parameters. (2) Methods: A fully validated chromatographic method was used to quantify mitotane concentration in plasma collected from adult patients, also considering the active metabolite ortho,para,dichlorodiphenylethene (o,p'-DDE). Statistical analyses were used to evaluate the sex influence on drugs pharmacokinetics. (3) Results: We found that sex resulted as predictive factor of plasma mitotane and o,p'-DDE concentrations and significantly influenced the attainment of the therapeutic target of mitotane, implying that female sex could be a risk factor of treatment failure. (4) Conclusions: These results suggest that mitotane therapy should be modulated according to patient sex. Furthermore, the proposed approach could contribute to facilitating and disseminating sex-specific pharmacology.
（1）背景：在临床环境中，有关性别的数据很少被研究。对于女性而言，体型和组成、激素变化、新陈代谢以及获得护理系统和治疗的机会等因素，可能会强烈影响药物治疗管理和治疗结果。为了强调这种与性别相关的差异，我们回顾性收集了接受米托坦治疗的肾上腺皮质癌患者的数据，然后评估了与性别相关的药代动力学参数。（2）方法：采用一种经过充分验证的色谱方法，对成年患者采集的血浆中的米托坦浓度进行定量分析，同时考虑活性代谢物邻，对 - 二氯二苯乙烯（o，p'-DDE）。采用统计分析方法评估性别对药物药代动力学的影响。（3）结果：我们发现性别是血浆米托坦和o，p'-DDE浓度的预测因素，并显著影响米托坦治疗靶点的实现，这意味着女性可能是治疗失败的危险因素。（4）结论：这些结果表明，米托坦治疗应根据患者性别进行调整。此外，所提出的方法可能有助于促进和推广针对性别的药理学。
