Table 2. Pharmacokinetic Characteristics of Lead Compounds 7 and 8a.
| dose route | parameter | 7 | 8 |
|---|---|---|---|
| Rat Pharmacokinetics | |||
| i.v. | dose (mg/kg) | 2.66 | 2.0 |
| plasma CL (mL/min/kg) | 77.0 ± 5.1 | 65.6 ± 7.4 | |
| Vss (L/kg) | 8.0 ± 2.7 | 16.8 ± 1.7 | |
| terminal t1/2 (h) | 3.0 ± 2.0 | 5.2 ± 0.07 | |
| p.o. | dose (mg/kg) | 13.3 | N.D. |
| F (%) | 1.0 | N.D. | |
| Mouse Pharmacokinetics | |||
| i.v. | dose (mg/kg) | 2.06 | N.D. |
| plasma CL (mL/min/kg) | 37.8 ± 8.9 | N.D. | |
| Vss (L/kg) | 3.2 ± 5.1 | N.D. | |
| terminal t1/2 (h) | 1.3 ± 0.2 | N.D. | |
| i.p. | dose (mg/kg) | 9.46 | 9.69 |
| Tmax (h) | 0.083–0.25 | 0.083–0.25 | |
| unbound Cmax (nM) | 221 ± 28 | 273 ± 37 | |
| F (%) | 83 | N.D. | |
a
Data are presented as mean ± SD for determinations in 3 animals. Bioavailability (F) was calculated from mean AUC according to F = (AUC,p.o./dose,p.o.)/(AUC,i.v./dose,i.v.).