Table 4.

Single-dose and steady-state plasma pharmacokinetic parameters of rucaparib following once- or twice-daily continuous oral administration (part 1, phase I dose escalation)

DosageNDayArithmetic mean Cmax (CV%), ng/mLMedian Tmax (range), hArithmetic mean AUC0–τ (CV%), ng·h/mLArithmetic mean CLss/F (CV%), L/hAR (CV%)Arithmetic mean t1/2 (CV%), h
40 mg QD31129 (28)2.5 (1–4)915aNRNA13.9 (57)
15138 (36)4 (1–4.05)1,810 (44)26.7 (59)1.68a25.7 (23)
80 mg QD31114 (41)1.5 (1–2.5)800 (27)NRNA11.0a
15175 (37)2.5 (2.5–2.57)1,740 (20)47.5 (23)2.33 (42)19.5a
160 mg QD41261 (51)4.0 (4–6.05)3,050 (51)NRNA19.9 (21)
15288 (29)b3.75 (2.5–4)b4,110 (33)b41.6 (29)b1.84 (31)b33.6 (12)b
300 mg QD31629 (37)2.5 (1–4.08)5,740 (38)NRNA15.2 (72)
15693 (76)2.53 (2.5–8)9,610 (83)46.7 (63)1.60 (53)29.8a
500 mg QD31949 (52)4 (4–4)11,000 (61)NRNA15.0 (32)
151390 (23)4 (4–4.17)19,900 (41)27.8 (35)1.94 (17)20.8 (38)
240 mg BID31219 (72)6 (4.05–6)2,800cNRNANRh
15971 (49)1.5 (1–4)10,700a27.3a5.44cNRh
360 mg BID81666 (58)3.23 (1.5–6)4,860 (58)dNRNANRh
151,300 (43)d3.3 (0–6.33)d9,430a40.4a4.08aNRh
480 mg BID911,150 (57)2.5 (1.5–4)8,810 (63)eNRNANRh
153,170 (69)e1.51 (0–6)e26,300 (73)d26.2 (63)d3.97 (38)fNRh
600 mg BID711,030 (61)4 (2.42–10)7,200 (66)gNRNANRh
152,420 (45)4 (2.53–10)21,400 (61)g58.6 (123)g3.23 (66)gNRh
840 mg BID311,380 (69)4 (2.5–8)13,200aNRNANRh
153,030 (NR)a4.04 (4–4.07)a29,000c29c1.47cNRh
  • 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.