Pharmacokinetic parameters of selective probe substrates are used to quantify the activity of an individual pharmacokinetic process (PKP) and the effect of perpetrator drugs thereon in clinical drug-drug interaction (DDI) studies. For instance, oral caffeine is used to quantify hepatic CYP1A2 activity, and oral dagibatran etexilate for intestinal P-glycoprotein (P-gp) activity. However, no probe substrate depends exclusively on the PKP it is meant to quantify. Lack of selectivity for a given enzyme/transporter and expression of the respective enzyme/transporter at several sites in the human body are the main challenges. Thus, a detailed understanding of the role of individual PKPs for the pharmacokinetics of any probe substrate is essential to allocate the effect of a perpetrator drug to a specific PKP; this is a prerequisite for reliably informed pharmacokinetic models that will allow for the quantitative prediction of perpetrator effects on therapeutic drugs, also in respective patient populations not included in DDI studies.

中文翻译：

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评估人体内药代动力学药物-药物相互作用：重新研究了药物代谢和药物运输的体内探针底物。

选择性探针底物的药代动力学参数可用于量化单个药代动力学过程（PKP）的活性，以及​​在临床药物-药物相互作用（DDI）研究中犯罪药物对其的影响。例如，口服咖啡因可用于定量测定肝脏CYP1A2的活性，而口服达吉巴坦酯可用于肠道P-糖蛋白（P-gp）的活性。但是，没有探针底物专门取决于要定量的PKP。对给定的酶/转运蛋白缺乏选择性以及相应的酶/转运蛋白在人体中几个位点的表达是主要的挑战。因此，详细了解单个PKP在任何探针底物的药代动力学中的作用对于将肇事者药物的作用分配给特定PKP是必不可少的。