Table 2.
The in vivo pharmacokinetic properties of CKD519 summarized as the results from non-compartmental analysis.
| Species | Administration Route | Sample Size | Sex | Dose (mg/kg) | Cmax (ng/mL) | Tmax (h) | AUClast (ng∙h/mL) |
CL/F * (mL/h) |
V/F * (mL) |
t1/2 (h) |
ke (h−1) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Hamster | Intravenous | 3 | F | 0.5 | 0.083 (0.083–0.083) |
8760 ± 635 | 6.36 ± 1.20 | 138 ± 89.9 | 16.9 ± 14.1 | 0.0616 ± 0.0446 | |
| Oral | 4 | F | 3 | 659 ± 89.3 | 3.5 (3–4) |
6140 ± 471 | 34.7 ± 3.08 | 1570 ± 163 | 31.5 ± 4.41 | 0.0223 ± 0.00294 | |
| 4 | F | 15 | 3250 ± 465 | 4 (3–4) |
18800 ± 4310 | 66.6 ± 20.1 | 2460 ± 162 | 26.8 ± 5.23 | 0.0268 ± 0.00613 | ||
| 4 | F | 45 | 3160 ± 614 | 4 (3–6) |
26700 ± 2330 | 145 ± 9.52 | 4330 ± 572 | 20.7 ± 1.76 | 0.0338 ± 0.00311 | ||
| Rat | Intravenous | 5 | F | 0.5 | 0.083 (0.083–0.083) | 3940 ± 585 | 28.9 ± 6.24 | 494 ± 126 | 12.0 ± 2.98 | 0.0677 ± 0.0214 | |
| Oral | 5 | F | 5 | 893 ± 231 | 3 (3–4) |
6640 ± 932 | 188 ± 28.6 | 2860 ± 1930 | 10.0 ± 4.78 | 0.0784 ± 0.0245 | |
| 5 | F | 15 | 2040 ± 448 | 2 (2–4) |
11600 ± 3240 | 323 ± 82.8 | 4770 ± 1740 | 10.1 ± 1.82 | 0.0701 ± 0.0107 | ||
| 5 | F | 45 | 184 ± 235 | 3 (2–5) |
12700 ± 1900 | 887 ± 140 | 10100 ± 1380 | 7.97 ± 0.782 | 0.0876 ± 0.00791 | ||
| Monkey | Intravenous | 4 | F | 0.1 | 0.1665 (0.083–0.25) |
5150 ± 1530 | 33.5 ± 20.3 | 3500 ± 1380 | 104 ± 80.0 | 0.0105 ± 0.00836 | |
| Oral | 4 | F | 1 | 752 ± 148 | 5.5 (5–6) |
8940 ± 954 | 230 ± 64.6 | 17600 ± 4000 | 59.9 ± 35.5 | 0.0140 ± 0.00570 | |
| 4 | F | 5 | 4700 ± 1100 | 7 (6–8) |
29500 ± 4840 | 309 ± 77.3 | 50500 ± 16900 | 125 ± 64.6 | 0.00707 ± 0.00412 | ||
| 4 | F | 30 | 10200 ± 2390 | 8 (8–8) |
79100 ± 15600 | 999 ± 123 | 67800 ± 44900 | 46.3 ± 26.8 | 0.0194 ± 0.0104 |
All values are presented as mean ± standard deviation except those for Tmax, which are the median (range); * For intravenous administration, CL and V were the estimated Cmax, maximum plasma concentration; Tmax, time to reach maximum plasma concentration; AUClast, area under the plasma concentration–time curve from time zero to time of the last measurable concentration; CL/F, oral clearance; V/F, apparent volume of distribution after oral administration; t1/2, half-life; ke, elimination rate constant.