Table 4.
PBPK model predictions: elagolix as a perpetrator
| Victim drug | Model stage | Elagolix dose | Mean Cmax ratio | Mean AUC∞ ratio | ||||
|---|---|---|---|---|---|---|---|---|
| Predicted | Observed | %PE (%) | Predicted | Observed | %PE (%) | |||
| Midazolam | Development | 150 mg QD | 0.75 | 0.81 | 8 (77) | 0.69 | 0.65 | 6 (46) |
| Application | 200 mg BID | 0.51 | Not applicable | 0.44 | Not applicable | |||
| Digoxin, day 1 | Development | 200 mg BID | 1.74 | 1.73 | 0.6 (42) | 1.22 | 1.32 | 8 (24) |
| Digoxin, day 10 | 200 mg BID | 1.73 | 1.71 | 1 (42) | 1.19 | 1.26 | 6 (21) | |
| Digoxin, day 1 | Application | 150 mg QD | 1.68 | Not applicable | 1.19 | Not applicable | ||
| Digoxin, day 10 | 150 mg QD | 1.73 | 1.19 | |||||
AUC∞ area under the curve from time zero to infinity, BID twice daily, Cmax maximum concentration, PBPK physiologically based pharmacokinetic, %PE percentage prediction error (acceptance criteria), QD once daily
PBPK simulation trial design for midazolam: elagolix administered for 16 days, midazolam administered on day 14 as a single dose
PBPK simulation trial design for digoxin: elagolix administered for 13 days, digoxin administered on days 1 and 10 as a single dose