Table 2.
Mean (%CV) Plasma and Urine PK Parameters of TAK-385 (Day 14, Multiple Oral Dosing [Part 2])
| Parameter | 20 mgb (Cohort 4) | 40 mgc (Cohort 3) | 80 mg (Cohort 1) | 180 mg (Cohort 2) |
|---|---|---|---|---|
| n | 6 | 6 | 6 | 6 |
| AUC0–24, ng · h/mL | 42.3 (24.9) | 121 (55.5) | 203 (26.9) | 704 (50.8) |
| Cmax, ng/mL | 3.91 (35.8) | 20.8 (64.0) | 35.6 (54.0) | 168 (97.4) |
| Cmin, ng/mL | 1.27 (25.4) | 2.74 (46.0) | 3.48 (31.2) | 11.4 (42.8) |
| Tmax, ha | 1.01 (0.50–1.50) | 1.59 (0.50–2.00) | 1.26 (0.50–4.00) | 1.50 (1.00–4.00) |
| t1/2, h | 64.5 (52.6)d | 49.4 (30.6) | 36.5 (17.4) | 35.8 (23.0) |
| R(AUC) | — | — | 1.92 (23.5) | 2.16 (43.0) |
| R(Cmax) | — | — | 1.52 (62.7) | 1.80 (37.7) |
| Fe, % | 1.44 (31.8) | 1.76 (38.6) | 1.89 (20.2) | 2.88 (45.6) |
| CLr (L/h) | 6.92 (29.5) | 6.42 (25.0) | 7.66 (17.4) | 7.43 (16.2) |
Abbreviations: AUC0–24, area under the plasma concentration time curve from time 0 to 24 h; CLr, renal clearance; Cmin, minimum observed plasma concentration over the 24-hour dosing interval (day 14); Fe, fraction of the dose excreted unchanged in urine; R(AUC), accumulation factor based on AUC; R(Cmax), accumulation factor based on Cmax; —, not applicable.
a
Median (range).
b
Loading doses of 320 mg on day 1, 240 mg on day 2, and 160 mg on day 3.
c
Loading dose of 360 mg on day 1.
d
n = 4.