Table 3.
Pharmacokinetic parameters for GS-DCBN and other metabolites in nasal wash samples from WT micea
DCBN dose (mg/kg), route | GS-DCBN | Gly-Cys-DCBN | Cys-DCBN | N-acetyl-Cys-DCBN | |
---|---|---|---|---|---|
AUC0–24 (h*pmol/ml) | 10, i.p. | 29.1 | 1.14 | 8.4 | 10.1 |
5, i.p. | 14.8 | 0.58 | 2.4 | 3.02 | |
1 × 4, s.c. | 6.2 | 0.29 | 3.4 | 3.4 | |
| |||||
t1/2 (h) | 10, i.p. | 3.3 | 3.2 | 6.4 | 7.3 |
5, i.p. | 4.9 | 4.8 | 13.9 | 2.6 | |
1 × 4, s.c. | 4.9 | 3.3 | 12.5 | 11.4 |
Two- to three-month old, male and female WT mice (n = 3–6 for each dose and time point) were treated with DCBN intraperitoneally (single injection at 5 or 10 mg/kg), or subcutaneously (four consecutive injections, each at 1 mg/kg, with 1.5-h intervals). Nasal-wash samples were collected from dissected nasal cavity of individual mice at various times (0.5–24 h) after the last dose, for LC-MS/MS analysis, as described in Materials and Methods. The mean levels of individual metabolites were used for calculation of pharmacokinetic parameters. Levels at individual time points are shown in Table 4.