Table 4.
Final population pharmacokinetic model parameter estimates for ManNAc and Neu5Ac in subjects with GNE myopathy
| Parameter | Final typical value estimate | %SEM |
|---|---|---|
| ka (h−1) | 0.256 | 15.2 |
| CLM/F (L/h) | 631 | 14.8 |
| VM/F (L) | 506 | 29.4 |
| M0 (ng/mL) | 61.1 | 12.0 |
| N0 (ng/mL) | 150 | 5.71 |
| kout (h−1) | 0.283 | 5.65 |
| SLP0 (ng/mL)−1 | 0.000619 | 29.1 |
| SLPSS (ng/mL)−1 | 0.00334 | 35.0 |
| kinc (h−1) | 0.0287 | 45.3 |
| tlag (h) | 0.254 | 26.4 |
| ksyn (μg/h)a | 38,554 | N/A |
| kpro (ng/mL·h)a | 40.9 | N/A |
| Relative ManNAc bioavailability (F) | ||
| F for 6 g dose | 1 | Fixed |
| F-Dose slope | − 0.405 | 39.0 |
| ω2 for ka | 0.0697 (26.4% CV) | 91.4 |
| ω2 for CLM/F | 0.0636 (25.2% CV) | 93.2 |
| ω2 for VM/F | 0.120 (34.6% CV) | 170 |
| ω2 for M0 | 0.0966 (31.1% CV) | 43.5 |
| ω2 for N0 | 0.0439 (21.0% CV) | 55.4 |
| ω2 for SLPSS | 0.383 (61.9% CV) | 130 |
| IOV on CLM/F | 0.0580 (24.1% CV) | 63.6 |
| σ2 CCV component | 0.102 (31.9% CV) | 8.13 |
| Additive component | 0.0370 (19.2% CV) | 5.68 |
CLM apparent clearance for ManNAc, F oral bioavailability, ka first-order oral absorption rate-constant for exogenously administered ManNAc, kinc first-order rate-constant of increase in the rate of conversion from ManNAc to Neu5Ac, kout first-order elimination rate constant for Neu5Ac (h−1), kpro zero-order production rate constant for Neu5Ac in precursor compartment, ksyn zero-order endogenous production rate constant for ManNAc, M0 initial endogenous plasma ManNAc concentration, N0 initial endogenous plasma Neu5Ac concentration, tlag absorption lag-time of ManNAc, VM/F apparent volume of distribution for ManNAc
aksyn and kpro are secondary parameters, where a typical value was calculated from typical values for other primary parameters