caffeine + dextromethorphan + midazolam + S-warfarin

This drug cocktail is a combination of four cytochrome P450 (CYP) enzyme probe substrates—caffeine (CYP1A2), S-warfarin (CYP2C9), dextromethorphan (CYP2D6), and midazolam (CYP3A)—developed and utilized by Eli Lilly and Company for clinical pharmacology research. It was specifically employed in a Phase 1 drug-drug interaction (DDI) study to assess the impact of multiple doses of abemaciclib (Verzenio) on the pharmacokinetics of these substrates in patients with advanced or metastatic cancer. By measuring the plasma concentrations of these probe drugs and their metabolites, researchers can determine the inhibitory or inductive effects of a test compound on major metabolic pathways simultaneously. The study demonstrated that abemaciclib did not have clinically meaningful effects on the pharmacokinetics of these CYP substrates, despite in vitro evidence suggesting potential downregulation.

Other names

drug cocktail-Eli Lilly and Company-advanced cancer-metastatic cancerCYP probe cocktailLilly DDI cocktailCYP substrate cocktail