Table 3.
Relative bias and precision of the ability of the Bayesian method using PKB-est to estimate the true patient parameters compared to that of the population mean data only. Random sparse simulated patient sampling (total of 1 to 3 samples per individual per regimen) was used for the Bayesian estimation for simulated drugs adhering to a one or two-compartment models. Compiled data includes all dose regimens available (intravenous bolus, intravenous infusion, oral dosing as single or repeated dose administration). The error and squared error of the differences in the population means and true values, and the Bayesian estimates and true values, were first calculated. The data shown are the means of the differences between those errors (me, mean error; mse, mean squared error) of the Bayesian minus the population errors, and the associated 95% confidence intervals.
| pharmacokinetic parameters | Difference of Bayesian minus population (95% CI) | |||
|---|---|---|---|---|
| Errors | One-compartment linear elimination | Two-compartment linear elimination | One-compartment nonlinear elimination | |
| CL/F | me | 0.063 (-0.13, 0.26) | 1.3 (-0.48, 3.2) | − |
| mse | -0.92 (-1.87, 0.033) | -250 (-340, -160)* | − | |
| Vdss/F | me | -0.25 (-1.6, 1.1) | 11 (1.0, 21) | -0.28 (-0.84, 0.27) |
| mse | -44 (-93, 5.5) | -6400 (-8500, -4200)* | 0.60 (-3.8, 5.0) | |
| Vc/F | me | − | 0.11 (-0.086, 0.30) | − |
| mse | − | -2.1 (-3.5, -0.65)* | − | |
| t½α | me | − | 0.047 (0.033, 0.062) | − |
| mse | − | -0.0056 (-0.010, -0.0017)* | − | |
| t½β | me | -1.3 (-3.5, 0.86) | 1.45 (0.419, 2.48)* | − |
| mse | -42 (-92, 8.5) | 57 (-16, 130) | − | |
| ka | me | -0.25 (-0.45, -0.050)* | -0.48 (-0.57, -0.40)* | -0.12 (-0.23, -0.020)* |
| mse | -0.56 (-0.77, -0.36)* | 0.11 (-0.17, 0.39) | 0.041 (-0.13, 0.21) | |
| Vmax | me | − | − | 0.034 (-0.54, 0.61) |
| mse | − | − | -8.1 (-11, -5.5)* | |
| km | me | − | − | -0.050 (-0.13, 0.028) |
| mse | − | − | 0.0933 (-0.0307, 0.217) | |
| CLint | me | − | − | 0.0408 (-0.112, 0.193) |
| mse | − | − | -0.568 (-0.854, -0.282)* | |
CL, clearance; Vdss, volume of distribution at steady state; Vc, volume of central compartment; t½α, distribution halflife; t½β, elimination half-life; ka, absorption rate constant; Vmax, maximum velocity; km, Michaelis-Menten constant; CLint, intrinsic clearance.