Abstract

1. A cocktail approach is a method to comprehensively evaluate the activity of cytochrome P450 enzymes (CYPs) by co-administering multiple CYP substrates. This is the first report that compares the results from a cocktail study to a single substrate separate administration study (single study) with concomitant administration of CYP inducers/inhibitors. The validity of a cocktail study for use as a quantitative drug-drug interactions (DDIs) assessment was evaluated.

2. We administered a cocktail drug (caffeine, losartan, omeprazole, dextromethorphan, midazolam) with rifampicin, cimetidine or fluvoxamine. A comparative analysis was performed between the results of a cocktail study and single studies. The results of single studies were obtained from a literature review and the trials of single substrate separate administration.

3. A strong positive correlation of the AUC ratio of all drugs between single studies and the cocktail study was obtained. The ratio of AUC change of 12 combinations converged to 0.82–1.09, and 2 combinations ranged between 0.74–1.32.

4. The differences in the degree of interaction between the single studies and cocktail study are acceptable to evaluate DDIs for almost all combinations. Our results indicate that a cocktail study is an adequate and quantitative evaluation method for DDIs.

抽象的

1. 鸡尾酒法是一种通过共同施用多种CYP底物来全面评估细胞色素P450酶（CYP）活性的方法。这是第一份报告，将鸡尾酒研究与单一底物单独给药研究（单项研究）与CYP诱导剂/抑制剂同时给药的结果进行了比较。评估了鸡尾酒研究用作定量药物-药物相互作用（DDI）评估的有效性。

2. 我们将鸡尾酒药物（咖啡因，氯沙坦，奥美拉唑，右美沙芬，咪达唑仑）与利福平，西咪替丁或氟伏沙明合用。在鸡尾酒研究和单项研究的结果之间进行了比较分析。单项研究的结果来自文献综述和单底物单独给药的试验。

3. 在单项研究和鸡尾酒研究之间，所有药物的AUC比率均具有很强的正相关性。12个组合的AUC变化比率收敛到0.82-1.09，而2个组合的AUC变化比率在0.74-1.32之间。

4. 单个研究和鸡尾酒研究之间相互作用程度的差异对于评估几乎所有组合的DDI都是可以接受的。我们的结果表明，鸡尾酒研究是DDI的适当且定量的评估方法。