Table 2.
Pharmacokinetic parameters of relugolix, unconjugated E2, unconjugated E1, and NET in pre-menopausal women after once-daily administration of relugolix plus E2/norethindrone acetate for 6 weeks
| Relugolix | E2 | E1 | NET | |
|---|---|---|---|---|
| Cmax (ng/mL or pg/mL) | 26 (21.4) | 46.8 (17.3) | 303 (137) | 5.21 (1.53) |
| tmax (h) | 3 (0.5, 6) | 3 (0.50, 12.00) | 4 (1, 8.08) | 1 (1, 2) |
| Cavg (ng/mL or pg/mL) | 6.53 (3.94) | 32.6 (10.9) | 186 (82.4) | 1.06 (0.474) |
| Ctrough (ng/mL or pg/mL) | 2.96 (1.74) | 20.8 (7.81) | 96.4 (45) | 0.302 (0.229) |
| AUC0–24 (ng*h/mL or pg*h/mL) | 157 (94.7) | 784 (262) | 4450 (1980) | 25.5 (11.4) |
| t1/2 (hr) | ND | 17.1 (4.03) | 13.9 (4.14) | 8.28 (1.87) |
Arithmetic means and standard deviations are shown except for tmax, where median and range (minimum, maximum) are shown. AUC0–24 is presented in ng*h/mL for relugolix and NET and in pg*h/mL for unconjugated E2 and unconjugated E1. Cmax is presented in ng/mL for relugolix and NET and in pg/mL for unconjugated E2 and unconjugated E1. The terminal elimination half-life for relugolix was not included, as the 24 h duration of sample collection in this study was deemed inadequate for capturing the elimination phase with a t1/2 of 61.5 h reported previously
AUC0–24 area under the concentration–time curve during a dosing interval (24), Cavg average concentration, Cmax maximum observed concentration, Ctrough trough concentration, E1 estrone, E2 estradiol, h hour, ND not determined, NET norethisterone, t1/2 terminal elimination half-life, tmax time to the maximum observed concentration