Table 1.
Pharmacokinetic parameters for methylprednisolone (MPL) and glucocorticoid receptor (GR) dynamics
| Parameter (units) | Definition | Estimate (% CV) |
|---|---|---|
| MPL pharmacokinetics | ||
| CL (L/h/kg) | Clearance | 2.93 (0.89) |
| CLD (L/h/kg) | Distribution clearance | 2.51 (1.94) |
| Vc (L/kg) | Central volume of distribution | 0.803 (0.97) |
| VT (L/kg) | Peripheral volume of distribution | 0.974 (1.51) |
| F | Bioavailability | 0.2 (0.94) |
| Fr | Fraction absorbed by ka1 | 0.725 (fixed) |
| ka1 (h−1) | Absorption rate constant | 1.82 (2.8) |
| ka2 (h−1) | Absorption rate constant | 0.54 (4.1) |
| Glucocorticoid receptor dynamicsa | ||
| ks,GRm (fmol/g/h) | Synthesis rate constant for GR mRNA | 3.2 |
| kd,GRm (h−1) | Degradation rate constant for GR mRNA | 0.12 |
| ks,GR (nM/h) (fmol/g)−1 | Synthesis rate constant for receptor | 0.84 |
| IC50,GRm (nM) | DRn for 50% inhibition of GR mRNA synthesis | 123.7 |
| kd,GR (h−1) | Degradation rate constant for receptor | 0.04 |
| kon (nM−1 h−1) | Association rate constant | 0.019 |
| fmpl | Unbound fraction of MPL | 0.23 |
| kre (h−1) | DRn loss rate constant | 0.402 |
| Rf | Fraction recycled | 0.69 |
| kT (h−1) | Translocation rate constant | 58.2 |
| GRm (0) (fmol/g) | GR mRNA initial concentration | 25.8 |
| GR(0) (nM) | Free cytosolic receptor initial concentration | 540.7 |
| DR(0) (nM) | Drug-receptor complex initial concentration | 0 |
| DRn(0) (nM) | Nuclear complex initial concentration | 0 |
a
Parameter values obtained from Hazra et al. [36]