Table 1.
Serum PK parameter estimates for single-dose M616 (multiple routes) in C57BL/6 mice obtained by NCA. Serum PK of M616 is not dose proportional. High bioavailability was observed for M616 based on comparison of AUC for IV vs. extravascular dose.
| Dose (mg/kg) | Route | AUCinf(nM*hr)/Dose (mg/kg)* |
MRTlast (hr) | CL* (mL/hr/kg) | Vss (mL/kg) | %F |
|---|---|---|---|---|---|---|
| 0.04 | IV | 1570 | 5.5 | 4.2 | 27.0 | |
| 0.4 | IV | 3230 | 15.0 | 2.1 | 31.1 | |
| 4 | IV | 14700 | 95.9 | 0.45 | 43.8 | |
| 4 | IP | 12800 | 103 | 0.52 | - | 87 |
| 4 | SC | 12200 | 102 | 0.55 | - | 83 |
*Note: There is a dose-dependent decrease in clearance indicating non-linearity. However, this violates the assumptions of the moment analysis method used to determine these parameters; hence, these estimates should be interpreted with caution.