Table 3.
Population pharmacokinetic/pharmacodynamic parameters for the Models 5 and 6: full glucose profile as the pharmacodynamic response
| Dose–full glucose profile model | Cpss–full glucose profile model | |||||
|---|---|---|---|---|---|---|
|
| ||||||
| Parameter | Estimate | RSE (%) | BSV (%CV) | Estimate | RSE (%) | BSV (%CV) |
| A0 (mmol/L) | 15.90 | 4.71 | 28.71 | 15.40 | 5.40 | 32.71 |
| A1 | 0.95 | 17.44 | 120.83 | 0.97 | 16.36 | 7.05 |
| B1 | 1.45 | 36.34 | 120.83 | 1.45 | 34.21 | 7.05 |
| A2 | –1.95 | –14.26 | 120.83 | –1.86 | –15.38 | 7.05 |
| B2 | 2.63 | 8.75 | 120.83 | 2.57 | 8.05 | 7.05 |
| Emax | 0.34 | 14.97 | 5.75 | 0.31 | 9.20 | 45.39 |
| ED50 (mg) | 2.21 | 29.46 | 15.13 | Derived ED50 = 2.26a | ||
| EC50 (mg/L) | – | – | – | 43.60 | 21.06 | 220.91 |
| Residual variability | – | – | – | – | – | – |
| Variance (%CV) | 0.02 (13%) | – | – | 0.02 (13%) | – | – |
Note:
a
Derived ED50 = EC50 × Cl/f × 24 where EC50 = 43.60 mg/L and drug clearance (CL/f)9 = 2.16 L/h.
Abbreviations: A0, baseline glucose concentration; A1, B1, A2, B2, coefficients of the harmonic function; Emax, maximum inhibition of glucose concentration; ED50, glibenclamide dose producing 50% inhibition of glucose concentration; EC50, glibenclamide concentration 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.