Table 2.
Observed and predicted pharmacokinetic parameters for children and adolescents with severe obesity.
| Parameter | Observed a | Predicted b | AFE |
|---|---|---|---|
| Cmax (mg/L) | 2.80 ± 0.978 (1.17 – 5.18); 1.56, 4.05 | 2.82 ± 0.577 (1.96 – 4.98); 1.56, 1.87 | 1.02 |
| AUC (h*mg/L) | 14.3 ± 5.00 (7.15 – 28.4); 10.4, 20.4 | 18.6 ± 6.10 (13.4 – 46.7); 10.0, 11.3 | 1.27 |
| CL/F (mL/min) | 1007 ± 326 (457 – 1817); 627, 318 | 737 ± 136 (278 – 973); 649, 574 | 0.786 |
| V/F (L) | 345 ± 150 (180 – 766); 125, 71.7 | 202 ± 30.3 (140 – 274); 185, 145 | 0.672 |
| eGFR (mL/min) | 131 ± 24.1 (91.7 – 188) c; 134, 102 | 84.5 ± 6.79 (70.4 – 94.8); 82.6, 70.4 | 0.654 |
Results for observed and predicted values for parameters are expressed as mean ± SD (range) for 27 children who received 1,000 mg doses of metformin twice daily and single values (in italics) for two subjects who received 500 mg doses twice daily. One patient who received 1,000 mg of metformin twice daily was excluded from the table due to missing data. AFE was calculated for the 29 paired values for PK parameters and 28 paired values for eGFR due to a missing observed estimate.
Observed values were calculated by noncompartmental analysis of observed plasma concentration-time data collected over 12 h following 6 months of metformin therapy.
Predicted values were calculated by noncompartmental analysis of simulated plasma concentration data at times used in the published sampling protocol.
Published values for eGFR (mL/min/1.73 m2) were converted to absolute eGFR (mL/min) using an estimate for body surface area (m2) calculated by the Haycock Equation.22
AFE, average fold error; AUC, area under the concentration-time curve calculated from 0 to 12 h at steady state; CL/F, oral clearance calculated as dose (mg) divided by AUC; Cmax, maximum plasma concentration of metformin at steady state; eGFR, estimated glomerular filtration rate; SD, standard deviation; V/F, apparent volume of distribution calculated as CL/F divided by the elimination rate constant.