TABLE 8.
Major pharmacokinetic parameters of selected macrolones in mice after intravenous and oral administrationa
| Compound | Intravenous bolusb |
Oral administrationc |
||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cmax (ng/ml) | AUC0–t (ng · h/ml) | AUC0–∞ (ng · h/ml) | CL (ml/min/kg) | Vss (liters/kg) | MRT (h) | t1/2 (h) | Cmax (ng/ml) | Tmaxd (h) | AUC0–t (ng · h/ml) | AUC0–∞ (ng · h/ml) | DNAUC0-∞ (ng · h/ml/mg/kg) | t1/2 (h) | F (%) | |
| 1e | 2,453 ± 788 | 3,307 ± 821 | ND | 5.3 ± 1.5 | 2.5 ± 0.4 | 8.0 ± 0.8 | 15.9 ± 4.3 | 49.0 ± 16.0 | 0.5 ± 0.1 | 124.7 ± 12.5 | ND | 12.5 ± 1.3 | ND | <1 |
| 7 | 781 ± 630 | 1,109 ± 242 | 1,349 ± 306 | 26.7 ± 4.5 | 15.0 ± 8.3 | 9.0 ± 3.6 | 8.2 ± 2.0 | 10.0 ± 8.0 | 2.0 ± 0.6 | 58.0 ± 73.9 | 98.4 ± 141.2 | 10.5 ± 15.0 | 8.5 ± 12 | 2 ± 2 |
| 19 | 1,887 ± 1,797 | 1,650 ± 227 | 1,794 ± 248 | 17.9 ± 2.7 | 8.2 ± 1.7 | 7.6 ± 0.9 | 7.9 ± 0.7 | 8.0 ± 3.0 | 2.0 ± 0.0 | 42.3 ± 7.1 | 47.3 ± 5.4 | 4.9 ± 0.6 | 2.5 ± 0.2 | <1 |
| 6 | 487 ± 173 | 2,998 ± 1,288 | ND | 12.9 ± 6.3 | 6.8 ± 2.9 | 9.0 ± 0.5 | 12.8 ± 2.3 | 140 ± 44 | 4.0 ± 0.0 | 1,767.8 ± 597.7 | ND | 176.8 ± 59.8 | 15.0 ± 3.0 | 12 ± 4 |
a
Three animals per group were tested. Abbreviations: Cmax, maximum concentration in plasma; AUC0–t, area under the plasma concentration-time curve from time zero to time t; AUC0–∞, area under the plasma concentration-time curve from time zero to infinity; CL, clearance; Vss, volume of distribution at steady state; MRT, mean residence time; t1/2, half-life; Tmax, time to Cmax; DNAUC0–∞, dose-normalized area under the plasma concentration-time curve from time zero to infinity; F, bioavailability; ND, not determined.
b
Target dose, 2 mg/kg.
c
Target dose, 10 mg/kg.
d
Tmax is expressed as the median.
e
Compound 1 administered at a dose of 1 mg/kg.