Table 3.
In vivo plasma and brain concentrations and pharmacokinetics of MRS2365 and its metabolite AST-004 in mice following intraperitoneal or intravenous administration of either MRS2365 or AST-004
| Compound administered | Compound monitored | Route of administration | Dose (mg/kg; μmol/kg) | Tissue | Concentration (ng/mL or ng/g) at time (h) | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 0 | 0.02 | 0.08 | 0.25 | 0.5 | 1 | 1.5 | 2 | 2.5 | |||||
| MRS2365 | MRS2365 | i.p. | 0.27; 0.5 | Plasma | - | - | < LLOQ | < LLOQ | < LLOQ | < LLOQ | - | < LLOQ | |
| i.v. | 0.27; 0.5 | Plasma | - | < LLOQ | < LLOQ | < LLOQ | < LLOQ | < LLOQ | - | < LLOQ | |||
| i.v. | 2.7; 5.0 | Plasma | - | < LLOQ | < LLOQ | - | - | - | - | - | |||
| Brain | - | - | < LLOQ | - | - | - | - | - | |||||
| MRS2365 | AST-004 | i.p. | 0.27; 0.5 | Plasma | - | - | 57.1 | 45.7 | 26.1 | 3.3 | - | 0.8 | - |
| Brain | - | - | 5.8 | 3.8 | 2.9 | < LLOQ | - | < LLOQ | - | ||||
| AST-004 | AST-004 | i.p. | 0.15; 0.5 | Plasma | - | - | 49.5 | 41.8 | 21.1 | 5.8 | - | 0.8 | - |
| Brain | - | - | 2.4 | 3.1 | 2.4 | < LLOQ | - | < LLOQ | - | ||||
| AST-004 | AST-004 | i.v. | 0.25; 0.8 | Plasma | - | - | 79.4 | 38.0 | 9.2 | 6.0 | 2.2 | 0.8 | 1.04 |
Results are the means of 3 mice per timepoint
LLOQ for MRS2365 was 5 ng/mL plasma or 5 ng/g brain tissue
LLOQ for AST-004 was 0.1 ng/mL plasma or 2.4 ng/g brain tissue
-Not sampled