Table 2.
Population pharmacokinetic parameters of the base model, excess weight covariate model, and final covariate model for metformin in 22 overweight and obese adolescents and results from a bootstrap analysis of the final model (995/1000 resamples successful)
| Parameter | Base model (RSE%) | Excess weight model (RSE%) | Final covariate model (RSE%) | Bootstrap (95% CI) |
|---|---|---|---|---|
| CL/F (l/min) | 1.21 (7) | – | – | – |
| CL/F = CL/F70kg × (WTfor age and length/70)0.75 + (Z × WTexcess) | ||||
| CL/F70kg | – | 1.16 (16) | – | – |
| Z | – | 0.011 (52) | – | – |
| CL/F = CL/F75.8kg × (1 + V × (TBW − 75.8) | ||||
| CL/F75.8 kg | – | – | 1.17 (6) | 1.18 (1.04–1.36) |
| V | – | – | 0.0138 (44) | 0.0126 (0.0035–0.0291) |
| V/F (L) | 488 (10) | 486 (10) | 485 (10) | 481.8 (396.8–607.8) |
| Ka (min−1) | 0.0253 (25) | 0.025 (25) | 0.0248 (25) | 0.0252 (0.0159–0.0563) |
| Interindividual variability (%) | ||||
| CL/F | 31.6 (29) [4] | 26.5 (32) [6] | 26.8 (31) [6] | 24.8 (5.5–40.3) |
| V/F | 37 (17) [14] | 36.5 (17) [14] | 36.2 (16) [14] | 33.8 (18.2–46.4) |
| Ka | 74.2 (21) [31] | 71.4 (22) [32] | 70.3 (22) [32] | 65.4 (26.7–132.9) |
| Residual variability (%) | ||||
| Proportional error | 21.7 (25) [19] | 21.8 (25) [18] | 21.8 (25) [18] | 22.0 (16.1–27.5) |
| OFV | − 134.4 | − 140.8 | − 141.0 | − 150.7 (− 204.4 to − 108.0) |
CI confidence interval, CL/F oral clearance, Ka absorption rate constant, OFV objective function value, RSE relative standard error, TBW total body weight, V/F oral volume of distribution, WTexcess excess body weight, WTfor age and length developmental weight