TABLE 3.
In vivo PK profiles of WX-081 and BDQa
| Compound | Species | Dosage (mg/kg) |
Vdss (L/kg) |
Cl (mL/min/kg) | t1/2 (h) |
Cmax (ng/mL) |
Tmax (h) |
AUC0-last (ng×h/m) | AUC0-inf (ng×h/m) | F (%) | At 96 h lung/plasma |
|---|---|---|---|---|---|---|---|---|---|---|---|
| BDQ | Mice | Iv. 1.0 | 6.21 | 7.76 | 21.3 | 2103 | 2158 | 27.1/1.31 | |||
| Po. 6.25 | 47.6 | 608 | 5.33 | 6038 | 6358 | 47.1 | 135/4.56 | ||||
| Rat | Iv. 1.0 | 10.3 | 8.67 | 37.6 | to | 1826 | 1931 | 62.9/1.89 | |||
| Po. 5.0 | 29.3 | 354 | 0.83 | 2614 | 2677 | 27.7 | 58.8/1.52 | ||||
| WX-081 | Mice | Iv. 1.0 | 10.4 | 3.59 | 46.3 | to | 3991 | 4797 | 241/12.4 | ||
| Po. 6.25 | 43.9 | 503 | 7.33 | 10155 | 11908 | 40.7 | 857/25.3 | ||||
| Rat | Iv. 1.0 | 9.2 | 8.25 | 25.6 | 2224 | 2351 | 235/3.61 | ||||
| Po. 5.0 | 29.8 | 328 | 1.00 | 4075 | 4312 | 36.7 | 337/4.74 | ||||
| Dog | Iv. 0.5 | 6.04 | 2.04 | 56.2 | 3610 | 4250 | |||||
| Po. 2.0 | 51.1 | 390 | 4.67 | 8500 | 9490 | 58.9 | |||||
| Po. 6.0 | 55.6 | 1080 | 5.33 | 20200 | 22800 | 46.6 | |||||
| Po. 20.0 | 57.6 | 1660 | 7.67 | 50400 | 58200 | 34.9 |
a
V, volume of distribution; Cl, clearance; t1/2, half-life; Cmax, maximum drug concentration; Tmax, peak time; AUC, concentration-time curve area; F, bioavailability; At 96 h lung/plasma, ratio of drug exposure of lung and plasma at 96 h. Both WX-081 and BDQ conducted PK studies in mice and rats, but only WX-081 was used for PK studies in dogs.