Table 2.
Population pharmacokinetic/pharmacodynamic parameters for Models 3 and 4: mean blood glucose as the pharmacodynamic response
| Dose–mean glucose model | Cpss–mean glucose model | |||||
|---|---|---|---|---|---|---|
|
| ||||||
| Parameter | Estimate | RSE (%) | BSV (%CV) | Estimate | RSE (%) | BSV (%CV) |
| E0 (mmol/L) | 16.70 | 5.74 | 27.07 | 16.70 | 5.74 | 26.94 |
| Emax | 0.34 | 14.32 | 50.99 | 0.34 | 14.49 | 50.89 |
| ED50 (mg) | 1.85 | 40.49 | 120.42 | Derived ED50 = 1.87a | ||
| EC50 (mg/L) | – | – | – | 36.00 | 42.78 | 108.17 |
| Residual variability | – | – | – | – | – | – |
| Variance (%CV) | 0.008 (8.75%) | – | – | 0.008 (8.92%) | – | – |
Note:
a
Derived ED50 = EC50 × Cl/f × 24, where EC50 = 36.00 mg/L and drug clearance (CL/f)9 = 2.16 L/h.
Abbreviations: E0, baseline glucose concentration; Emax, maximum inhibition of glucose concentration; EC50, glibenclamide concentration producing 50% inhibition of glucose concentration; ED50, glibenclamide dose producing 50% inhibition of glucose concentration; RSE, relative standard error of the estimate; BSV, between-subject variability; CV, coefficient of variation; Cpss, steady-state glibenclamide concentration.