Table 4.
Pharmacokinetic parameters of CGA, CCGA, NCGA, CA, CA-3-G, and CA-4-G after a single oral administration of YRA-1909 at doses of 25, 50, and 100 mg/kg (equivalent to 1.2, 2.4, and 4.8 mg/kg CGA; 0.275, 0.55, and 1.10 mg/kg NCGA; 0.87, 1.74 and 3.48 mg/kg CCGA) and repeated administration of 50 mg/kg YRA-1909 for seven days to male rats (mean ± SD).
| Compounds | PK Parameters | Dose of YRA-1909 (mg/kg) | |||
|---|---|---|---|---|---|
| Single Oral Dosing | 7-Day Repeated Oral Dosing | ||||
| 25 (n = 6) | 50 (n =12) | 100 (n = 6) | 50 (n = 6) | ||
| CGA | Cmax (ng/mL) | 3.11 ± 0.96 | 5.59 ± 1.61 | 8.73 ± 2.83 | 4.85 ± 1.25 |
| Tmax 1 (h) | 0.25 (0.083–0.25) | 0.25 (0.083–0.5) | 0.25 | 0.25 (0.083–0.5) | |
| AUClast (ng∙h/mL) | 4.29 ± 1.92 | 8.16 ± 3.65 | 14.38 ± 5.06 | 7.54 ± 1.86 | |
| t1/2 (h) | NC | NC | 1.52 ± 0.79 | NC | |
| MRT (h) | 1.19 ± 0.22 | 1.48 ± 0.50 | 1.67 ± 0.63 | 1.48 ± 0.18 | |
| CCGA | Cmax (ng/mL) | NC | 4.01 ± 0.82 | 5.64 ± 1.45 | 3.81 ± 0.72 |
| Tmax 1 (h) | NC | 0.25 (0.083–0.5) | 0.25 (0.083–0.25) | 0.25 (0.083–0.5) | |
| AUClast (ng∙h/mL) | NC | 4.15 ± 4.10 | 6.26 ± 4.70 | 3.35 ± 3.42 | |
| MRT (h) | NC | 0.61 ± 0.55 | 0.84 ± 0.65 | 0.56 ± 0.57 | |
| NCGA | Cmax (ng/mL) | 0.70 ± 0.12 | 1.18 ± 0.26 | 1.69 ± 0.43 | 1.08 ± 0.28 |
| Tmax 1 (h) | 0.17 (0.083–0.5) | 0.25 (0.083–0.5) | 0.25 (0.083–0.25) | 0.25 (0.083–0.25) | |
| AUClast (ng∙h/mL) | 0.81 ± 0.22 | 1.61 ± 0.90 | 3.40 ± 1.97 | 1.60 ± 0.79 | |
| MRT (h) | 0.68 ± 0.30 | 1.00 ± 0.58 | 1.66 ± 0.91 | 1.09 ± 0.55 | |
| CA | Cmax (ng/mL) | 3.92 ± 1.47 | 7.31 ± 2.12 | 16.72 ± 5.45 | 6.07 ± 0.94 |
| Tmax 1 (h) | 1.25 (1.0–1.5) | 0.25 (0.083–1.0) | 0.25 (0.25–2.0) | 0.17 (0.083–2.0) | |
| AUClast (ng∙h/mL) | 5.60 ± 1.30 | 12.40 ± 4.03 | 29.73 ± 15.24 | 11.75 ± 3.31 | |
| MRT (h) | 0.90 ± 0.11 | 1.29 ± 0.31 | 1.74 ± 0.87 | 1.26 ± 0.33 | |
| CA-3-G | Cmax (ng/mL) | 69.09 ± 25.06 | 129.05 ± 30.41 | 238.55 ± 97.46 | 132.18 ± 26.70 |
| Tmax 1 (h) | 0.38 (0.25–1.0) | 0.38 (0.25–1.0) | 0.25 (0.25–1.0) | 0.38 (0.25–1.0) | |
| AUClast (ng∙h/mL) | 111.15 ± 37.32 | 208.77 ± 80.46 | 405.33 ± 188.56 | 216.38 ± 25.06 | |
| t1/2 (h) | 1.05 ± 0.38 | 0.93 ± 0.23 | 0.82 ± 0.23 | 0.88 ± 0.19 | |
| MRT (h) | 1.49 ± 0.52 | 1.33 ± 0.24 | 1.68 ± 0.69 | 1.33 ± 0.12 | |
| CA-4-G | Cmax (ng/mL) | 3.86 ± 0.94 | 6.97 ± 1.91 | 9.38 ± 2.56 | 7.77 ± 1.85 |
| Tmax 1 (h) | 1.0 (1.0–1.5) | 0.75 (0.25–2.0) | 1.0 (0.5–2.0) | 1.5 (1.0–2.0) | |
| AUClast (ng∙h/mL) | 6.04 ± 0.77 | 14.95 ± 4.03 | 25.59 ± 10.84 | 18.95 ± 3.30 | |
| MRT (h) | 1.01 ± 0.18 | 1.48 ± 0.27 | 1.77 ± 0.46 | ± 0.23 | |
1 Tmax presented median value with the range in parentheses. NC: Not calculable.