Table 2. Pharmacokinetic values of (S)-YK-4-279 were obtained in SD rats following oral gavage administration of racemic, (S)-YK-4-279 or (R)-YK-4-179.
| Treatment group (Target dose) | Gender | Observed Cmax (¼M) | Observed Tmax (hr) | Terminal Elimination Half-Life (hr) | Apparent Clearance (mL/hr/kg) | AUClast (hr*¼M) | AUC∞ (hr*¼M) | Absolute Bioavailability (%) |
|---|---|---|---|---|---|---|---|---|
| Group 4: Racemic YK-4-279 (25 mg/kg) | Male (n=9) | 0.142 | 1.00 | 3.84 | 90,300 | 0.563 | 0.754 | 2.83 |
| Female (n=9) | 0.513 | 0.500 | 1.56 | 52,200 | 1.07 | 1.31 | 5.06 | |
| Group 5: (S)-YK-4-279 (25 mg/kg) | Male (n=9) | 0.261 | 1.00 | 3.59 | 63,200 | 0.833 | 1.08 | 2.06 |
| Female (n=9) | 0.620 | 2.00 | 1.86 | 30,000 | 2.14 | 2.28 | 4.07 | |
| Group 6: (R)-YK-4-279 (25 mg/kg) | Male (n=9) | BLOQ1 | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ |
| Female (n=9) | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ | |
| Group 7 Racemic YK-4-279 (50 mg/kg) | Male (n=9) | 0.241 | 2.00 | 4.23 | 116,000 | 1.04 | 1.18 | 2.21 |
| Female (n=9) | 0.647 | 0.500 | 1.97 | 43,400 | 3.09 | 3.14 | 6.07 | |
| Group 8: (S)-YK-4-279 (50 mg/kg) Male (n=9) | 0.380 | 2.00 | 3.94 | 55,400 | 1.78 | 2.46 | 2.35 | |
| Female (n=9) | 1.04 | 2.00 | 2.37 | 28,400 | 4.64 | 4.81 | 4.29 | |
| Group 9: (R)-YK-4-279 (50 mg/kg) | Male (n=9) | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ |
| Female (n=9) | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ | BLOQ |
1. BLOQ: below the limit of quantitation