TABLE 2.
Pharmacokinetic parameters for plasma AαC and its metabolites in LCN and WT mice at a low dose of AαC (1.36 mg/kg)1
| Strain | Analytes | Tmax
(h) |
Cmax
(ng/ml) |
t1/2
(h) |
AUC0-6h
(h*ng/ml) |
CL/F (ml/h) |
|---|---|---|---|---|---|---|
| WT | AαC | 1.0 ± 0 | 1.4 ± 0.9 | 1.7 ± 0.9 | 2.5 ± 1.3 | 15300 ± 5690 |
| LCN | AαC | 1.0 ± 0 | 21.8 ± 13.6a |
1.4 ± 0.5 | 45.2 ± 16.9a | 884 ± 378a |
| WT | AαC-N2-Glu | 1.0 ± 0 | 19.2 ± 13.5 | 1.4 ± 0.7 | 40.5 ± 16.6 | 985 ± 372 |
| LCN | AαC-N2-Glu | 1.0 ± 0 | 74.3 ± 48.6a |
1.5 ± 0.8 | 195 ±78.7a | 207 ± 100a |
| WT | AαC-3-OSO3H | 1.0 ± 0 | 74.6 ± 31.5 | 5.9 ± 6.1 | 165.6 ± 47.6 | 180 ± 140 |
| LCN | AαC-3-OSO3H | 1.0 ± 0 | 177 ± 73.0a | 2.5 ± 1.7 | 438 ± 118a | 76.0 ± 39.2b |
1
Plasma levels of AαC, AαC-N2-Glu and AαC-3-OSO3H were determined after a single dose of AαC at 1.36 mg/kg via oral gavage. Plasma samples were obtained at various times after dosing. Values represent means ± S.D. (n = 5).
a
P < 0.001;
b
P < 0.01;
compared to the corresponding WT group (Student’s t-test or Mann-Whitney Rank test )