Table 2.
Summary of PK parameters of rosuvastatin and oral contraceptives with and without rucaparib (PK analysis population)
| PK parameter | Rosuvastatin | Ethinylestradiol | Levonorgestrel | |||
|---|---|---|---|---|---|---|
| Without rucaparib (n = 17) | With rucaparib (n = 18) | Without rucaparib (n = 18) | With rucaparib (n = 18) | Without rucaparib (n = 18) | With rucaparib (n = 18) | |
| Cmax, ng/mL | ||||||
| n | 17 | 16 | 18 | 17 | 18 | 17 |
| Mean (SD) | 20.5 (25.4) | 25.4 (21.0) | 0.0792 (0.0311) | 0.0893 (0.0443) | 3.32 (1.13) | 3.77 (1.70) |
| GM (%CV) | 13.0 (116) | 18.1 (107) | 0.0732 (44.3) | 0.0784 (59.7) | 3.17 (30.7) | 3.43 (47.3) |
| Median (range) | 10.2 (2.6–106) | 18.1 (5.1–72.7) | 0.0734 (0.0255–0.151) | 0.0756 (0.025–0.167) | 3.29 (1.88–7.08) | 3.48 (1.46–7.23) |
| AUC0–last, h × ng/mL | ||||||
| n | 17 | 16 | 18 | 17 | 18 | 17 |
| Mean (SD) | 193 (156) | 266 (209) | 0.804 (0.370) | 1.24 (0.484) | 59.7 (35.3) | 86 (39.9) |
| GM (%CV) | 145 (95.9) | 200 (95.9) | 0.714 (57.4) | 1.15 (43.8) | 52.9 (49.6) | 77.5 (51.5) |
| Median (range) | 141 (21.9–552) | 208 (42.7–850) | 0.775 (0.231–1.54) | 1.18 (0.486–2.15) | 45.3 (30.3–149) | 80.4 (28.1–182) |
| AUC0–inf, h × ng/mL | ||||||
| n | 16 | 16 | 11 | 12 | 10 | 7 |
| Mean (SD) | 192 (158) | 276 (217) | 0.994 (0.257) | 1.49 (0.505) | 72.7 (43.9) | 109 (49.9) |
| GM (%CV) | 145 (94.0) | 210 (93.0) | 0.962 (28.4) | 1.41 (35.1) | 64.0 (53.0) | 102 (40.6) |
| Median (range) | 145 (23.0–559) | 212 (46.1–894) | 1.00 (0.537–1.37) | 1.37 (0.806–2.37) | 55.4 (39.1–168) | 87.3 (62.7–214) |
| tmax, h | ||||||
| n | 17 | 16 | 18 | 17 | 18 | 17 |
| Median (range) | 1.5 (0.50–4.00) | 2.0 (0.50–6.00) | 1.00 (0.50–2.00) | 1.50 (1.00–47.5) | 1.51 (0.97–4.00) | 1.50 (1.00–47.5) |
| t1/2, h | ||||||
| n | 16 | 16 | 16 | 16 | 16 | 15 |
| Mean (SD) | 20.6 (13.1) | 18.5 (8.49) | 17.0 (5.69) | 30.0 (25.7) | 41.1 (15.9) | 50.0 (19.7) |
| GM (%CV) | 17.5 (64.4) | 16.6 (51.8) | 15.9 (40.9) | 24.8 (63.4) | 38.5 (38.5) | 46.6 (40.4) |
| Median (range) | 17.6 (5.17–60.5) | 16.1 (6.25–32.8) | 18.1 (7.29–25.1) | 27.1 (9.27–122) | 37.1 (22.4–75.7) | 43.6 (23.6–84.5) |
| CL/F, L/h | ||||||
| N | 16 | 16 | 11 | 12 | 10 | 7 |
| Mean (SD) | 191 (201) | 128 (109) | 32.4 (9.82) | 22.4 (7.54) | 2.57 (1.01) | 1.57 (0.531) |
| GM (%CV) | 138 (94.0) | 95.3 (93.0) | 31.2 (28.4) | 21.2 (35.1) | 2.34 (53.0) | 1.48 (40.6) |
| Median (range) | 138 (35.8–870) | 94.3 (22.4–434) | 30.0 (21.8–55.8) | 21.8 (12.7–37.2) | 2.71 (0.891–3.84) | 1.72 (0.701–2.39) |
| VZ/F, L | ||||||
| n | 16 | 16 | 11 | 12 | 10 | 7 |
| Mean (SD) | 4620 (3730) | 2960 (2250) | 792 (175) | 684 (217) | 113 (43.9) | 82.8 (30.0) |
| GM (%CV) | 3490 (94.4) | 2280 (85.0) | 772 (24.9) | 653 (32.7) | 103 (55.6) | 77.6 (42.7) |
| Median (range) | 3730 (792–15,200) | 1840 (815–8100) | 772 (418–1140) | 620 (385–1000) | 114 (30.6–188) | 85.6 (35.9–132) |
If percentage extrapolation was > 20% or Rsq was ≤ 0.80, then AUC0–inf, CL/F, and VZ/F were excluded from summary statistics. If Rsq was ≤ 0.80, then t1/2 was excluded from summary statistics
%CV coefficient of variation in percent, AUC area under the concentration–time curve, AUC0–inf AUC extrapolated from time 0 to infinity, AUC0–last AUC from time 0 up to the last time point with a quantifiable concentration, CL/F apparent total clearance of drug after oral administration, Cmax maximum plasma concentration, GM geometric mean, h hours, N total number of patients, n number of assessed patients, PK pharmacokinetics, Rsq R-squared, SD standard deviation, t1/2 half-life, tmax median time to maximum concentration, VZ/F apparent volume of distribution during terminal phase