Table 3.
Summary of PK parameters of MGX (PK analysis set)
| Parameter, geometric mean (% CV) | IV cohort (600 mg q24h) n = 9 |
PO cohort (500 mg q24h) n = 9 |
|---|---|---|
| Primary | ||
| First-order absorption rate constant (1/h) | — | 1.49 (141.3) |
| Clearance (mL/h) | 3696 (29.7) | 3879 (21.5) |
| Central compartment volume of distribution (L) | 61.4 (43.3) | 110 (66.3) |
| Intercompartmental clearance (mL/h) | 16 203 (200) | 5130 (322) |
| Peripheral compartment volume of distribution (L) | 188 (79.0) | 78.9 (113) |
| Secondary | ||
| Cmax (ng/mL) | 8033 (24.9) | 5610 (37.5) |
| Primary | ||
| AUC (ng·h/mL) | 124 217 (29.7) | 98 634 (21.5) |
| Distribution half-life (h) | 1.52 (112) | 4.43 (163) |
| Elimination half-life (h) | 60.9 (43.6) | 47.4 (52.2) |
| Volume of distribution, steady state (L) | 270 (43.7) | — |
| Observed | ||
| Cmax Day 7 (ng/mL) | 7876 (23.9) | 6319 (29.6) |
| Cmax Day 14 (ng/mL) | 6254 (38.9)a | 5616 (35.3) |
The CL and V values are CL/F and V/F for PO treatment where F = bioavailability. Primary and secondary parameters are from fitting the compartmental model to the data. Primary parameters were used to fit the model, and secondary parameters were calculated from primary parameters. Observed parameters were taken from observed data. AUC, area under the curve over a dosing interval at steady-state; Cmax, maximum plasma concentration; CV, coefficient of variation; h, hour; IV, intravenous; MGX, manogepix; PK, pharmacokinetic; PO, oral; q24h, once a day
n = 8 [1 participant (IV cohort) received only 10 doses; Cmax Day 14 could not be calculated for that participant].