TABLE 3.
Plasma 873140 pharmacokinetic parameters after single and repeat oral doses of 873140 hydrochloride saltd
| Day and treatment | Geometric mean for pharmacokinetic parameter indicated (95% CI)
|
|||||
|---|---|---|---|---|---|---|
| AUC(0-∞) (ng · h/ml) | Cmax (ng/ml) | Tmax (h) | Tlag (h) | t1/2 (h) | CL/F (liters/min) | |
| Day 1 | ||||||
| 200 mg (n = 8)b | 90.6 (56.3-146) | 18.8 (13.31-26.42) | 2.75 (1.00-6.00) | 0.25 (0.25-0.50) | 1.97 (1.59-2.45) | 34.6 (21.5-55.7) |
| 400 mg (n = 8)b | 206 (113-377) | 34.9 (19.3-63.3) | 3.75 (2.00-5.00) | 0.13 (0-0.75) | 1.92 (1.58-2.32) | 30.4 (16.6-55.4) |
| 600 mg (n = 8)b | 292 (164-520) | 47.9 (31.4-73.1) | 5.00 (4.00-12.00) | 0.13 (0-1.00) | 2.49 (1.53-4.07) | 32.2 (16.6-55.4) |
| 800 mg (n = 8)b | 438 (181-1057) | 80.0 (39.2-163) | 5.00 (4.00-10.00) | 0.00 (0-0.50) | 1.99 (1.49-2.65) | 28.7 (11.9-69.2) |
| Day 8 | ||||||
| 200 mg BID (n = 8)c | 125 (95.2-163) | 27.3 (19.3-38.6) | 1.75 (1.00-4.00) | 0.0 | 2.48 (2.01-3.05) | 25.2 (19.2-32.9) |
| 400 mg BID (n = 7)c | 228 (156-333) | 55.2 (38.3-79.5) | 4.00 (2.00-5.00) | 0.0 | 2.45 (2.05-2.92) | 27.5 (18.9-40.1) |
| 600 mg BID (n = 8)c | 283 (204-392) | 64.5 (47.5-87.5) | 2.75 (2.00-5.00) | 0.0 | 2.23 (1.56-3.19) | 33.3 (24.0-46.1) |
| 800 mg BID (n = 8)c | 409 (253-660) | 123 (67.8-223) | 2.02 (1.50-5.00) | 0.0 | 2.09 (1.59-2.76) | 30.7 (19.0-49.5) |
a
Dose strengths represent mg of 873140 in hydrochloride salt form. Medians and ranges are presented for Tlag and Tmax.
b
AUC(0-∞) and t1/2 values are based on cohorts of 5 (400 mg, 600 mg), 6 (200 mg), or 7 (800 mg) subjects.
c
t1/2 values are based on cohorts of 5 (200, 400, 800 mg BID) or 4 (600 mg BID) subjects.
d
Data for day 1 are for single doses; data for day 8 are for repeat (twice daily) doses.