Table 2.
Population pharmacokinetic model-derived estimates and bootstrap results for pharmacokinetic parameters of metformin
| Final model parameter | Median (%RSE)a |
Median (90% Cl)b |
|---|---|---|
| Total clearance (CL/F; I/h) | 78.4 (6) | 77.5 (70–87) |
| Central volume of distribution (Vc/F; I) | 76.8(15) | 76.7 (53–95) |
| Peripheral flow (Q/F; I/h) | 18.1 (9) | 18.8(16–32) |
| Peripheral volume of distribution (Vp/F; I) | 413(43) | 419(286–3,293) |
| Mean transit time (h) | 0.207(24) | 0.2033(0.14–0.37) |
| Absorption rate(ka; 1/h) | 0.312(5) | 0.31 (0.28–0.34) |
| Interindividual variability (% variance) | ||
| Between-subject variability (CL) | 50(10) | 50 (40–60) |
| Between-subject variability (Vc) | 45(13) | 45 (34–64) |
| Between-subject variability (Q) | 41 (23) | 40 (27–49) |
| Covariance of parameters | ||
| Correlation between total clearance and central volumeof distribution (CL-V) |
0.05 (5) | 0.10 (−0.33–0.29) |
| Residual error model | ||
| Studies 6112/6113 | ||
| Proportional error (%) | 14(12) | 0.14(0.11–0.16) |
| Additive error | 0.02(32) | 0.02(0.01–0.02) |
| Study 865 | ||
| Proportional error (%) | 12(6) | 12(11–13) |
| Additive error | 0.01 | - |
| Study 787 | ||
| Proportional error (%) | 21(13) | 20(16–25) |
| Additive error | 0.01 (20) | 0.007(0.003–0.012) |
| Patient data | ||
| Proportional error (%) | 20(13) | 0.2(0.16–0.24) |
| Additive error | 0.01 | - |
a
Typical value of pharmacokinetic parameter in final model. RSE, relative standard error (%), also known as the precision of the population pharmacokinetic parameter estimate.
b
Confidence interval (CI) forthe population pharmacokinetic parameterfollowing bootstrap results. Reference ethnicity of model output is African Americans, due to the high proportion of African Americans in the cohort.