Increased risk of drug-drug interaction for rosuvastatin and digoxin
Figure 4 shows the application of NMP to assess drug-drug interactions in cirrhotic and non-cirrhotic livers. Figure 6A shows the results of these studies in which different drugs were used to inhibit the uptake and /or excretion of the drug cocktail from the previous section. In both cirrhotic and non-cirrhotic livers, rosuvastatin and digoxin AUC0-tau and Cmax was increased upon co-administration of a perpetrators cocktail (Figure 6B,C). However, the drug-drug interaction, expressed as an increase in Cmax, and increase in AUCR (i.e. ratio AUC of victim drug with and without inhibitors over 120 min) was more profound but not significant in the non-cirrhotic livers than the cirrhotic livers. More specifically, the AUCR for rosuvastatin and digoxin was 5.6 (IQR: 3.1-13.3) and 8.1 (IQR: 4.6-20.5) respectively in non-cirrhotic livers compared to 1.4 (IQR: 0.9-1.9) and 2.2 (IQR: 1.3-3.5) respectively in cirrhotic livers. No increase in AUC0-tau and Cmax was observed for the low-hepatic extraction ratio drugs furosemide and metformin