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抗癌药物的药理动力学中的性别差异:系统性审查
J Delahousse1, A D Wagner2, S Borchmann3
1Department of Pharmacology, Gustave Roussy, Villejuif, France.
患者的性别显著影响抗癌药物药理动力学 (PK),影响药物的活性和安全性. 建议针对性别的剂量策略,以优化治疗疗效和降低风险.
科学领域:
- 药理学 药理学是指药理学的学科.
- 在瘤学瘤学.
- 临床药房 临床药房
背景情况:
- 患者的性别是影响抗癌药物药理动力学 (PK) 的已知因素,影响治疗的有效性和安全性.
- 这些基于性别的PK差异的程度和临床相关性在很大程度上仍然未被描述.
研究的目的:
- 系统地审查和识别男性和女性患者之间的PK显著差异,以获得FDA批准的抗癌药物.
- 评估性对药物清除和低谷度的影响.
主要方法:
- 在2022年1月之前发表的FDA批准的抗癌药物 (不包括激素药物) 临床研究 (n ≥10) 的系统综述.
- 显著的PK差异定义为清除或低谷度≥20%的变化.
- 使用NIH工具评估方法质量;审查遵循PRISMA 2020指南.
主要成果:
- 选了99种抗癌药物;最终分析包括112篇文章和8份监管文件.
- 在14种药物中发现了显著的PK差异,在其他8种药物中存在潜在的显著差异.
- 没有研究报告了基于性别的摘要,将PK变异与临床结果 (疗效/安全) 联系起来.
结论:
- 在广泛使用的抗癌药物中存在显著的基于性别的PK差异,包括5-甲,多克索鲁比辛和帕克利塔塞尔.
- 制定特定于性别的剂量策略对于改善这些药物的风险益益比至关重要.
- 建议根据性别进行进一步的PK-药理动力学分析,与FDA的Project Optimus指南保持一致.
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