Table 2.
Single dose study: TAK-683 main PK parameters in plasma and urine, after a single bolus dose
| Geometric mean (%CV) | ||||||
|---|---|---|---|---|---|---|
| 0.01 mg (n = 7) | 0.03 mg (n = 7) | 0.1 mg (n = 7) | 0.3 mg (n = 7) | 1.0 mg (n = 7) | 2.0 mg (n = 7) | |
| Plasma | ||||||
| Cmax (pg ml−1) | 58.6 (4.17) | 125.4 (27.68) | 603.2 (56.97) | 1396.9 (43.74) | 5 404.8 (41.23) | 10 940.0 (26.08) |
| AUC(0,∞) (pg ml−1 h) | 173.0 (20.11) | 414.4 (21.64) | 2080.0 (21.04) | 5988.8 (23.04) | 20 027.7 (16.47) | 34 565.7 (21.12) |
| t1/2 (h) | 2.92 (52.96) | 3.07 (38.14) | 6.05 (18.87) | 7.41 (26.93) | 8.92 (31.75) | 8.81 (33.06) |
| tmax (h), median, (range) | 0.25 (0.08–0.50) | 0.25 (0.08–0.50) | 0.25 (0.25–0.50) | 0.25 (0.25–0.52) | 0.50 (0.25–0.50) | 0.50 (0.25–0.50) |
| Urine | ||||||
| CLR (l h−1) | 2.366 (312.23) | 0.072 (–) | 0.035 (209.14) | 0.036 (72.71) | 0.048 (224.65) | 0.065 (83.67) |
| Ae(0,t) (μg) | 0.039 (277.71) | 0.004 (–) | 0.077 (171.33) | 0.213 (81.57) | 0.960 (194.03) | 2.240 (72.76) |
| fe (%) | 3.913 (277.71) | 0.125 (–) | 0.077 (171.33) | 0.071 (81.57) | 0.096 (194.03) | 0.112 (72.76) |
AUC(0, ∞), area under the plasma concentration–time curve from time 0 to infinity; Ae(0,t), total amount of drug excreted in urine from time 0 to t; Cmax, maximum observed plasma concentration; CLR, renal clearance CLR = Ae(0,t)/AUC(0,t); fe, Fraction of drug excreted in urine, fe = (Ae(0,t)/dose) × 100; t1/2, terminal half-life, n(2)/λz; tmax, time to reach Cmax; %CV, percent coefficient of variation.