The probe-drug cocktail approach to efficiently investigate transporter-mediated drug–drug interactions is attracting increasing research interest. In previous clinical trials, we optimized a four-component cocktail comprising digoxin, furosemide, metformin, and rosuvastatin.

The cocktail was validated by investigating the effects of four prototypical inhibitors of drug transport (verapamil, rifampin, cimetidine, probenecid) on probe-drug systemic exposure in healthy subjects. The observed inhibitor effects on cocktail drug exposure proved for the first time sufficient sensitivity and specificity of a drug transporter cocktail.

The proposed cocktail is ready to be used as an effective, safe, and reliable option to investigate clinical drug–drug interaction potential involving key transporters (P-glycoprotein, organic anion transporter 1, organic anion transporter 3, organic cation transporter 2, multidrug and toxin extrusion protein 1, multidrug and toxin extrusion protein 2-K, organic anion transporting polypeptide 1B1, organic anion transporting polypeptide 1B3, and breast cancer resistance protein) in the development of new drugs.