Table 2.
Summary of plasma pexidartinib and ZAAD-1006a pharmacokinetic parameters
| Pharmacokinetic parameter | Statistic | Esomeprazole Study | Itraconazole study | Rifampin study | Probenecid study | ||||
|---|---|---|---|---|---|---|---|---|---|
| Pexidartinib alone | Pexidartinib + esomeprazole | Pexidartinib alone | Pexidartinib + itraconazole | Pexidartinib alone | Pexidartinib + rifampin |
Pexidartinib alone | Pexidartinib + probenecid | ||
| Pexidartinib | |||||||||
| Cmax, ng/mL | n | 16 | 16 | 16 | 13 | 16 | 16 | 15 | 16 |
|
Mean (SD) |
6694 (1795) |
3123 (1143) |
4215 (851) |
6650 (2192) |
5261 (1939) |
3499 (1051) |
5377 (1763) |
5583 (1844) |
|
| tmax, h | n | 16 | 16 | 16 | 13 | 16 | 16 | 15 | 16 |
|
Median (range) |
3.0 (1.50–4.50) |
2.0 (1.50–4.00) |
2.5 (1.50–4.50) |
2.0 (1.50–4.50) |
2.5 (1.50–4.00) |
3.0 (1.50–4.50) |
2.5 (1.50–4.50) |
2.5 (1.50–3.50) |
|
| AUC∞, ng•h/mL | n | 16 | 16 | 16 | 13 | 15 | 16 | 15 | 16 |
|
Mean (SD) |
107,585 (28,219) |
58,054 (17,514) |
76,045 (17,211) |
139,842 (37,676) |
96,697 (28,517) |
35,446 (12,046) |
77,509 (28,477) |
118,899 (27.1) |
|
| t½, h | n | 16 | 16 | 16 | 13 | 15 | 16 | 15 | 16 |
|
Mean (SD) |
25.3 (7.11) |
26.7 (8.96) |
24.2 (3.71) |
28.8 (4.18) |
25.4 (4.93) |
16.8 (4.21) |
21.5 (18.2–42.3) |
26.7 (19.5–38.6) |
|
| ZAAD-1006a | |||||||||
| Cmax, ng/mL | n | 16 | 16 | 16 | 13 | 16 | 16 | 15 | 16 |
|
Mean (SD) |
5464 (1339) |
2593 (827) |
3903 (842) |
6019 (1435) |
4780 (2110) |
6574 (2753) |
4403 (1331) |
4284 (1191) |
|
| tmax, h | n | 16 | 16 | 16 | 13 | 16 | 16 | 15 | 16 |
|
Median (range) |
4.25 (3.00–5.00) |
4.25 (2.00–4.50) |
4.50 (2.00–5.00) |
4.50 (2.50–8.00) |
4.50 (2.50–4.50) |
4.50 (3.00–8.00) |
4.50 (2.50–5.00) |
6.98 (3.50–11.9) |
|
| AUC∞, ng•h/mL | n | 16 | 16 | 16 | 13 | 16 | 16 | 15 | 16 |
|
Mean (SD) |
134,977 (37,097) |
71,677 (24,690) |
117,211 (29,221) |
246,701 (66,704) |
131,507 (53,792) |
75,577 (37,180) |
97,684 (33,889) |
208,436 (48,136) |
|
| t½, h | n | 16 | 16 | 16 | 13 | 16 | 16 | 15 | 16 |
|
Mean (SD) |
25.3 (6.92) |
26.7 (7.59) |
24.0 (4.28) |
30.0 (4.11) |
26.0 (5.70) |
16.1 (4.55) |
25.1 (7.28) |
28.6 (4.89) |
|
| Metabolite-to-parent ratio | |||||||||
| Cmax, MW- adjusted ratio (%) | n | 16 | 16 | 16 | 13 | 16 | 16 | 15 | 16 |
|
Mean (SD) |
55.9 (11.3) |
60.6 (10.6) |
66.2 (13.6) |
67.9 (21.4) |
64.7 (15.9) |
131.9 (36.4) |
85.2 (23.4) |
79.5 (17.6) |
|
| AUC∞, MW-adjusted ratio (%) | n | 16 | 16 | 16 | 13 | 15 | 16 | 15 | 16 |
|
Mean (SD) |
89.0 (14.6) |
86.7 (11.6) |
109.6 (20.7) |
126.3 (25.1) |
95.8 (27.1) |
149.5 (47.6) |
128.4 (31.2) |
181.4 (44.6) |
|
AUC∞ area under the plasma concentration–time curve from 0 to infinity, Cmax maximum plasma concentration, MW molecular weight, SD standard deviation, t½ terminal elimination half-life, tmax time to Cmax