Table 3.
Plasma ManNAc and Neu5Ac PK Parameters after a Single Dose of Oral ManNAc to Fasted GNE Myopathy Subjects (Baseline adjusted concentrations were used in the PK calculation).
| Dose | Tmax1 | Cmax2 | Cmax Ratio | Mean AUCinf3 | AUCinf Ratio | CL/F3 | t1/21 | MRT∞3 | ||
|---|---|---|---|---|---|---|---|---|---|---|
| (g) | (h) | (ng/mL) | Dose Compared | Ratio | (ng.h/mL) | Dose Compared | Ratio | (L/h) | (h) | (h) |
| Plasma ManNAc | ||||||||||
| 3 | 2.0 | 1451 | 6/3 g | 0.9 | 8244±4090 | 6/3 g | 1.2 | 418±147 | 2.2 | 5.6±0.8 |
| 6 | 2.5 | 1336 | 10/6 g | 1.9 | 9552±3441 | 10/6 g | 1.5 | 691±215 | 2.6 | 6.4±2.3 |
| 10 | 2.0 | 2585 | 10/3 g | 1.8 | 14161±5793 | 10/3 g | 1.7 | 827±375 | 2.4 | 5.3±0.5 |
| Plasma Unconjugated Free Neu5Ac | ||||||||||
| 3 | 10.0 | 115 | 6/3 g | 1.6 | 2147±405 | 6/3 g | 1.9 | ND | 5.5 | 17.9±3.1 |
| 6 | 11.0 | 181 | 10/6 g | 0.8 | 4171±1785 | 10/6 g | 0.7 | ND | 7.8 | 22.9±5.5 |
| 10 | 8.0 | 143 | 10/3 g | 1.2 | 3007±1162 | 10/3 g | 1.4 | ND | 7.2 | 19.2±4.5 |
1
Median
2
Geometric Mean
3
PK calculations (mean ± SD) were conducted with baseline adjustment by subtracting ManNAc or Neu5Ac concentrations at t=0 for each subject.
Abbreviations: Cmax: maximum observed plasma concentration, Tmax: time to Cmax, AUCinf: area under the plasma concentration versus time curve from time 0 (pre-dose) to time infinity, CL/F: apparent systemic clearance, t½: terminal-phase half-life, MRT: mean residence time, ND: not determined.