个体化治疗中使用药物遗传学指南已经显示出潜力，通过启用基因型匹配的剂量和药物选择，有助于减少药物反应的个体间变异性。然而，其他重要因素，如患者性别，在确定毒性和疗效个体特征方面可能会与药物遗传学强烈互动，但在规划药物治疗时仍然很少考虑。 文献表明男性和女性对药物的反应不同，女性更容易出现毒性反应，并且在标准剂量下对药物的血浆暴露有所不同。最近的研究表明，药物遗传变异在不同性别中的预测价值可能不同，例如使用阿片类药物、ACE抑制剂或质子泵抑制剂治疗的情况。特别感兴趣的是用于癌症治疗的氟脲嘧啶治疗。已经描述了女性患者的毒性显著增加，同时也注意到特定的DPYD和TYMS多态性具有更为显著的影响。本文综述了性别特异性药物遗传学领域的主要研究结果。意义声明：药物反应的个体间变异性是药物学中一个新兴的问题。患者的遗传特征以及其性别可能在识别更容易出现不良药物反应或疗效差的患者方面发挥作用。本文综述了性别和药物遗传学相互作用在处理个体变异性方面的当前研究状况。版权所有 © 2023年美国药理学和实验治疗学会。

The use of pharmacogenetic guidelines in personalizing treatments has shown the potential to reduce interindividual variability in drug response by enabling genotype-matched dosing and drug selection. However, other important factors, such as patient gender, may interact strongly with pharmacogenetics in determining the individual profile of toxicity and efficacy, but are still rarely considered when planning pharmacological treatment. The literature indicates that males and females respond differently to drugs, with women being at higher risk for toxicity and having different plasma exposure to drugs at standard doses. Recent studies have shown that pharmacogenetic variants may have different predictive value in different sexes, as in the case of treatment with opioids, ACE inhibitors, or proton pump inhibitors. Of particular interest is the case of treatment with fluoropyrimidines for cancer. A significant increase in toxicity has been described in female patients, with a more pronounced effect of specific DPYD and TYMS polymorphisms also noted. This manuscript reviews the major findings in the field of sex-specific pharmacogenomics. Significance Statement Interindividual variability in drug response is an emerging issue in pharmacology. The genetic profile of patients, as well as their gender, may play a role in the identification of patients more exposed to the risk of adverse drug reactions or poor efficacy. This article reviews the current state of research on the interaction between gender and pharmacogenetics in addressing interindividual variability.Copyright © 2023 American Society for Pharmacology and Experimental Therapeutics.