Table 3.
Parameter estimates for the population pharmacokinetics model of metformin and results of the bootstrap validation of the final model
| Parameter (units) | Estimate (%RSE) | CV% | Bootstrap median (95% CI)* |
|---|---|---|---|
| Fixed effects | |||
| V/F (L) | 28.8 (17.5) | 63.7 | 29.2 (1.00, 61.9) |
| CL/F (L/hr) | 68.1 (5.48) | 28.4 | 68.3 (59.6, 79.3) |
| ka1 (hr−1) | 0.335 (17.1) | 32.1 | 0.292 (0.124, 0.689) |
| ka2 (hr−1) | 0.139 (13.6) | 56.9 | 0.141 (0.00139, 47.8) |
| tx (hr) | 2.28 (3.48) | 2.20 (0.0318, 2.85) | |
| f | 0.446 (13.4) | 0.468 (0.280, 0.985) | |
| Effect of eGFR on CL/F | 1.10 (34.5) | 1.08 (0.008, 1.84) | |
| Random effects | |||
| Inter-subject variability (ω2) | |||
| V/F | 0.406 (37.7) | 0.498 (0.120, 12.8) | |
| CL/F | 0.0804 (38.3) | 0.0811 (0.0306, 0.218) | |
| V/F~CL/F | 0.129 (48.7) | 0.158 (0.0269, 1.11) | |
| ka1 | 0.103 (38.3) | 0.0804 (1×10−6, 0.227) | |
| ka2 | 0.324 (39.2) | 0.327 (1×10−6, 224) | |
| Residual error | |||
| Std. deviation (mg/L) | 1.58 (16.9) | 1.14 (1.09, 1.24) | |
*
Results of 1000 bootstrap re-samples of the final model.
RSE, relative standard error; CV, coefficient of variation; CI, confidence interval
V/F, apparent volume of distribution; CL/F, apparent total clearance of metformin; ka1, absorption rate constant at the first absorption site; ka2, absorption rate constant at the second absorption site; tx, time for the second fraction of the drug to begin to be absorbed; f, fraction of metformin absorbed at the first absorption site; eGFR, estimated glomerular filtration rate