Single-dose and steady-state plasma pharmacokinetic parameters of rucaparib following once- or twice-daily continuous oral administration (part 1, phase I dose escalation)
| Dosage | N | Day | Arithmetic mean Cmax (CV%), ng/mL | Median Tmax (range), h | Arithmetic mean AUC0–τ (CV%), ng·h/mL | Arithmetic mean CLss/F (CV%), L/h | AR (CV%) | Arithmetic mean t1/2 (CV%), h |
|---|---|---|---|---|---|---|---|---|
| 40 mg QD | 3 | 1 | 129 (28) | 2.5 (1–4) | 915a | NR | NA | 13.9 (57) |
| 15 | 138 (36) | 4 (1–4.05) | 1,810 (44) | 26.7 (59) | 1.68a | 25.7 (23) | ||
| 80 mg QD | 3 | 1 | 114 (41) | 1.5 (1–2.5) | 800 (27) | NR | NA | 11.0a |
| 15 | 175 (37) | 2.5 (2.5–2.57) | 1,740 (20) | 47.5 (23) | 2.33 (42) | 19.5a | ||
| 160 mg QD | 4 | 1 | 261 (51) | 4.0 (4–6.05) | 3,050 (51) | NR | NA | 19.9 (21) |
| 15 | 288 (29)b | 3.75 (2.5–4)b | 4,110 (33)b | 41.6 (29)b | 1.84 (31)b | 33.6 (12)b | ||
| 300 mg QD | 3 | 1 | 629 (37) | 2.5 (1–4.08) | 5,740 (38) | NR | NA | 15.2 (72) |
| 15 | 693 (76) | 2.53 (2.5–8) | 9,610 (83) | 46.7 (63) | 1.60 (53) | 29.8a | ||
| 500 mg QD | 3 | 1 | 949 (52) | 4 (4–4) | 11,000 (61) | NR | NA | 15.0 (32) |
| 15 | 1390 (23) | 4 (4–4.17) | 19,900 (41) | 27.8 (35) | 1.94 (17) | 20.8 (38) | ||
| 240 mg BID | 3 | 1 | 219 (72) | 6 (4.05–6) | 2,800c | NR | NA | NRh |
| 15 | 971 (49) | 1.5 (1–4) | 10,700a | 27.3a | 5.44c | NRh | ||
| 360 mg BID | 8 | 1 | 666 (58) | 3.23 (1.5–6) | 4,860 (58)d | NR | NA | NRh |
| 15 | 1,300 (43)d | 3.3 (0–6.33)d | 9,430a | 40.4a | 4.08a | NRh | ||
| 480 mg BID | 9 | 1 | 1,150 (57) | 2.5 (1.5–4) | 8,810 (63)e | NR | NA | NRh |
| 15 | 3,170 (69)e | 1.51 (0–6)e | 26,300 (73)d | 26.2 (63)d | 3.97 (38)f | NRh | ||
| 600 mg BID | 7 | 1 | 1,030 (61) | 4 (2.42–10) | 7,200 (66)g | NR | NA | NRh |
| 15 | 2,420 (45) | 4 (2.53–10) | 21,400 (61)g | 58.6 (123)g | 3.23 (66)g | NRh | ||
| 840 mg BID | 3 | 1 | 1,380 (69) | 4 (2.5–8) | 13,200a | NR | NA | NRh |
| 15 | 3,030 (NR)a | 4.04 (4–4.07)a | 29,000c | 29c | 1.47c | NRh |
Abbreviations: AR, accumulation ratio based on AUC; AUC0–τ, area under the plasma concentration–time curve from 0 to the end of dosing interval (τ = 24 hours for QD; τ = 12 hours for BID; for BID dosing, concentration at 12 hours was calculated by extrapolation from last observed concentration in the same dosing interval); BID, twice daily; CV, coefficient of variation; NA, not available; NR, not reportable; QD, once daily.
↵an = 2.
↵bn = 3.
↵cn = 1.
↵dn = 6.
↵en = 8.
↵fn = 5.
↵gn = 4.
↵ht1/2 is too long to allow for accurate estimate in BID dosing.