Multi-factorial pharmacokinetic interactions: unraveling complexities in precision drug therapy.
Multi-factorial pharmacokinetic interactions: unraveling complexities in precision drug therapy.
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DOI：
10.1080/17425255.2021.1867105
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发表时间：
2021-04
影响因子：
4.3
通讯作者：
Clarke J
中科院分区：
文献类型：
--
作者：
Bechtold B;Clarke J
精准药物治疗需要考虑药代动力学（PK）个体间变异的相关因素（即药物遗传学、疾病、多药和天然产品使用），这些因素可能导致亚治疗或不良反应。虽然这些单独的因素都可以改变受害者药物的PK，但多因素的相互作用可能导致叠加、协同或相反的作用。确定这些复杂的多因子效应的大小和方向需要了解每种药物的限速冗余和/或顺序PK过程。药物代谢酶和/或转运体的扰动是单因子和多因子PK相互作用的组成部分。单因素PK相互作用的例子包括基因-药物（药理学）、疾病-药物、药物-药物和天然产物-药物相互作用。多因子PK相互作用的例子包括药物-基因-药物、天然产物-基因-药物、基因-基因-药物、疾病-天然产物-药物和疾病-基因-药物相互作用。多因子相互作用的清晰解释可能会因研究设计、受害者药物PK的复杂性以及对受害者药物PK的不完整机制理解而变得复杂。将复杂的多因子PK相互作用纳入精确药物治疗需要临床决策工具、有意的PK研究设计、药物代谢酶和转运蛋白分数贡献确定、系统和计算方法(例如：基于生理的药代动力学模型)，以及进展性疾病的PK表型。
Precision drug therapy requires accounting for pertinent factors in pharmacokinetic (PK) inter-individual variability (i.e., pharmacogenetics, diseases, polypharmacy, and natural product use) that can cause sub-therapeutic or adverse effects. Although each of these individual factors can alter victim drug PK, multi-factorial interactions can cause additive, synergistic, or opposing effects. Determining the magnitude and direction of these complex multi-factorial effects requires understanding the rate-limiting redundant and/or sequential PK processes for each drug. Perturbations in drug metabolizing enzymes and/or transporters are integral to single- and multi-factorial PK interactions. Examples of single factor PK interactions presented include gene-drug (pharmacogenetic), disease-drug, drug-drug, and natural product-drug interactions. Examples of multi-factorial PK interactions presented include drug-gene-drug, natural product-gene-drug, gene-gene-drug, disease-natural product-drug, and disease-gene-drug interactions. Clear interpretation of multi-factorial interactions can be complicated by study design, complexity in victim drug PK, and incomplete mechanistic understanding of victim drug PK. Incorporation of complex multi-factorial PK interactions into precision drug therapy requires advances in clinical decision tools, intentional PK study designs, drug metabolizing enzyme and transporter fractional contribution determinations, systems and computational approaches (e.g., physiologically-based pharmacokinetic modeling), and PK phenotyping of progressive diseases.
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影响因子：
5.4
作者：
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通讯作者：
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作者：
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作者：
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通讯作者：
International Transporter Consortium