Drug interaction studies of therapeutic proteins or monoclonal antibodies
Drug interaction studies of therapeutic proteins or monoclonal antibodies
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DOI：
10.1177/0091270007308616
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发表时间：
2007-12-01
影响因子：
2.9
通讯作者：
Green, Martin David
中科院分区：
文献类型：
--
作者：
Mahmood, Iftekhar;Green, Martin David
药物相互作用可以改变药物的药代动力学和/或药效学。在药物动力学药物相互作用中，一种或多种药物的浓度被另一种药物改变。药物浓度的这种变化可能是由于吸收、分布、代谢或消除的变化所致。药效学相互作用可导致药物的相加、协同或拮抗作用。药物相互作用研究经常与常规药物(小分子)进行，但很少与大分子(治疗性蛋白质或单抗)进行药物相互作用研究。这主要是因为大多数大分子不被细胞色素P450系统代谢，其消除机制复杂。然而，几项研究表明，干扰素可以对细胞色素P450系统产生影响，当与干扰素一起服用时，可能会改变传统药物的药代动力学和药效学。因此，评估其他类型的大分子(细胞因子、白介素类、单抗)对药物代谢酶的影响是很重要的。还必须研究常规药物对大分子药物动力学和药效学的影响。本综述包括了几项与大分子药物相互作用的研究，并强调了这些研究对所涉及药物的药代动力学和/或药效学的影响。
Drug interactions can alter the pharmacokinetics and/or pharmacodynamics of a drug. In pharmacokinetic drug interactions, the concentrations of 1 or more drugs are altered by another. This change in concentration in a given drug may be due to changes in absorption, distribution, metabolism, or elimination. The pharmacodynamic interaction can lead to additive, synergistic, or antagonistic effects of a drug. Drug interaction studies are regularly conducted with conventional drugs (small molecules), but very few drug interaction studies have been performed with macromolecules (therapeutic proteins or monoclonal antibodies). This is mainly because most macromolecules ore not metabolized by the cytochrome P450 system, and their mechanism of elimination is complex. However, it has been shown in several studies that interferons can have an impact on the cytochrome P450 system that may alter the pharmacokinetics and pharmacodynamics of a conventional drug when given with interferons. Therefore, it is important to evaluate the effect of other classes of macromolecules (cytokines, interleukins, monoclonal antibodies) on drug-metabolizing enzymes. It is also imperative that the effects of conventional drugs on the pharmacokinetics and pharmacodynamics of macromolecules be conducted. The present review encompasses several drug interaction studies that were conducted with macromolecules and highlights the impact of these studies on the pharmacokinetics and/or pharmacodynamics of the involved drugs.