Table 3. Pharmacokinetic parameters of TAK-285 after single and multiple oral dosing of TAK-285.
|
Dose level of TAK-285
|
||||||
|---|---|---|---|---|---|---|
| Parameters | 50 mg q.d.a | 50 mg b.i.d.a | 100 mg b.i.d.a | 200 mg b.i.d.a | 300 mg b.i.d.a | 300 mg b.i.d.b |
| Single dosing | ||||||
| N | 4 | 3 | 3 | 4 | 4 | 5–6 |
| Cmax (ng ml–1) | 214 (30.3) | 234 (55.6) | 379 (91.8) | 965 (194) | 1350 (469) | 983 (545) |
| AUC0–∞ (ng × h ml–1) | 1730 (423) | 1970 (648) | 2820 (1190) | 9530 (4150) | 11 500 (4750) | 9210 (3840) |
| Tmax (h) | 1.49 (1.00–2.00) | 1.00 (1.00–2.02) | 2.00 (1.00–4.00) | 2.48 (2.00–4.00) | 2.00 (2.00–2.00) | 2.03 (2.00–4.00) |
| t1/2 (h) | 7.27 (2.58) | 6.45 (0.642) | 9.43 (4.85) | 6.57 (1.16) | 7.50 (0.968) | 6.10 (2.21) |
| Multiple dosing c | ||||||
| N | 3 | 3 | 3 | 3 | 3 | 5–6 |
| Cmax (ng ml–1) | 260 (57.9) | 358 (51.1) | 774 (344) | 2420 (156) | 3700 (680) | 2810 (1120) |
| AUC0–tau (ng × h ml–1) | 2210 (973) | 2720 (778) | 6090 (3140) | 1700 (3970) | 30 900 (6750) | 26 400 (9840) |
| Tmax (h) | 2.00 (2.00–2.02) | 2.05 (2.00–2.05) | 2.00 (2.00–3.00) | 2.00 (1.00–2.05) | 2.00 (2.00–2.02) | 2.97 (0.500–6.00) |
| t1/2 (h) | 8.69 (2.87) | 7.49 (0.738) | 7.79 (0.760) | 6.95 (1.21) | 8.25 (1.61) | 11.1 (3.65) |
| R (Cmax) | 1.20 (0.342) | 1.55 (0.205) | 2.00 (0.613) | 2.70 (0.829) | 3.12 (1.22) | 3.62 (2.05) |
| R (AUC) | 1.35 (0.331) | 1.96 (0.148) | 2.79 (0.792) | 3.22 (0.677) | 3.92 (1.69) | 4.59 (2.14) |
Abbreviations: AUC=area under the plasma concentration-time curve from time zero to infinity (0–∞) or to dosing interval (0–tau); b.i.d.= twice daily; Cmax=maximal observed plasma concentration after dosing; q.d.= once daily; R=accumulation ratio of Cmax or AUC between multiple versus single dosing; R (AUC)=AUC0−tau (treatment day D)/AUC0−12 (treatment day 1) (dose escalation cohort: D=21, repeated administration cohort: D=28); Tmax=time to reach the maximal plasma concentration; t1/2=estimated terminal-phase half-life.
All parameters are reported as mean (±s.d.) values, except for Tmax that is reported as a median (range) value.
a
Dose escalation cohort.
b
Repeated administration cohort.
c
Day 21 or day 28.