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