Table 1.
Population pharmacokinetic/pharmacodynamic parameters for Models 1 and 2: fasting blood glucose as the pharmacodynamic response
| Dose–fasting glucose model | Cpss–fasting glucose model | |||||
|---|---|---|---|---|---|---|
|
| ||||||
| Parameter | Estimate | RSE (%) | BSV (%CV) | Estimate | RSE (%) | BSV (%CV) |
| E0 (mmol/L) | 14.10 | 6.35 | 29.05 | 14.30 | 6.04 | 27.40 |
| Emax | 0.37 | 37.47 | 48.68 | 0.39 | 22.64 | 55.50 |
| ED50 (mg) | 4.56 | 77.19 | 0.01 | Derived ED50 = 4.41a | ||
| EC50 (mg/L) | 85.20 | 26.29 | 0.04 | |||
| Residual variability | ||||||
| Variance (%CV) | 0.02 (15%) | 0.02 (14%) | ||||
Note:
a
Derived ED50 = EC50 × Cl/f × 24, where EC50 = 85.20 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.