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caffeine + warfarin + vitamin K + omeprazole + dextromethorphan + midazolam
- Development stage
- Unknown
- Lead developer
- Roche
- Modality
- Small Molecules
- Administration
- Oral
01
Overview
This drug cocktail is a research tool consisting of five cytochrome P450 (CYP450) probe substrates: caffeine (CYP1A2), warfarin (CYP2C9), omeprazole (CYP2C19), dextromethorphan (CYP2D6), and midazolam (CYP3A4). It was utilized by Hoffmann-La Roche in a Phase 1 clinical trial (NCT01001299) to assess the potential for vemurafenib (Zelboraf) to cause drug-drug interactions by inhibiting or inducing these specific metabolic enzymes in patients with metastatic melanoma. The cocktail allows for the simultaneous evaluation of multiple metabolic pathways by measuring the pharmacokinetics of each substrate in the presence and absence of the test drug. Vitamin K is typically included to mitigate the anticoagulant effects of warfarin during the study.
- Other names
- CYP450 probe cocktailCYP-450 probe cocktailCYP 450 probe cocktailRoche CYP450 cocktailFive-probe drug cocktail
02
Targets
VKORC1 (Vitamin K epoxide reductase complex subunit 1)CYP1A2 (Cytochrome P450 1A2)CYP2C19 (Cytochrome P450 2C19)CYP2C9 (Cytochrome P450 family 2 subfamily C member 9)CYP2D6 (Cytochrome P450 2D6)CYP3A4 (Cytochrome P450 3A4)
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