Table 2.
Descriptive summary of plasma and urine talazoparib PK parameters following administration of multiple oral doses of talazoparib, by renal function group (Day 22, PK analysis population)
| Parameter summary statisticsa by renal function group | ||||
|---|---|---|---|---|
| Normal renal function | Mild renal impairment | Moderate renal impairment | Severe renal impairment | |
| Plasma PK | n = 6 | n = 7 | n = 8b | n = 7 |
| AUC0–24 [ng•h/mL] | 94.88 (27) | 106.5 (40) | 135.7 (45) | 249.8 (30) |
| Cmax [ng/mL] | 8.609 (35) | 9.568 (58) | 11.33 (45) | 16.30 (34) |
| Ctrough [ng/mL] | 2.172 (34) | 2.680 (52) | 3.893 (45) | 7.917 (44) |
| Tmax [h] | 1.50 (0.97–4.00) | 2.00 (0.50–4.00) | 1.49 (0.47–4.02) | 3.88 (0.50–8.00) |
| CL/F [L/h] | 5.270 (27) | 4.698 (40) | 3.687 (45) | 2.000 (30) |
| Rac | 4.465 (3.44–15.6) | 4.070 (3.05–9.15) | 5.970 (3.97–10.6) | 7.170 (5.66–14.9) |
| fu [%] | 29.85 (24) | 31.54 (10) | 29.09 (9) | 32.49 (30) |
| AUC0–24u [ng•h/mL] | 28.33 (32) | 33.59 (31) | 39.47 (47) | 81.17 (36) |
| Cmaxu [ng/mL] | 2.570 (42) | 3.019 (47) | 3.295 (48) | 5.296 (30) |
| CLu/F [L/h] | 17.66 (32) | 14.89 (31) | 12.68 (47) | 6.164 (36) |
| Urine PK | n = 5 | n = 7 | n = 7 | n = 7c |
| Ae0–24 [mg] | 0.258 (23) | 0.232 (20) | 0.164 (54) | 0.201 (34) |
| Ae20–4 [%] | 51.7 (23) | 46.4 (20) | 32.8 (54) | 40.1 (34) |
| CLr [L/h] | 2.74 (37) | 2.18 (57) | 1.33 (97) | 0.709 (35) |
Ae0–24 amount of drug excreted in urine from time 0 to 24 h postdose, AUC0–24 area under the concentration-time curve from 0 to 24 h, AUC0–24u unbound AUC0–24, CL/F apparent oral clearance, CLu/F unbound CL/F, CLr renal clearance, Cmax maximum observed plasma concentration, Cmaxu unbound Cmax, Ctrough plasma trough (predose) concentration, CV% percentage coefficient of variation, fu fraction of unbound drug in plasma, PK pharmacokinetics, Rac accumulation ratio, Tmax time to Cmax
aGeometric mean (geometric CV%) for all parameters except median (range) for Tmax and Rac
bn = 7 for Rac
cn = 5 for CLr