Table 1.
Optimized physiologically‐based pharmacokinetic model parameters (k a, k trans, and R MATE/dif) after fitting to the oral metformin doses of 1,500 and 250 mg using differing βkidney values
| 1,500 mg metformin | |||||
|---|---|---|---|---|---|
| Observed6 | βkidney | ||||
| 0.1 | 0.3 | 0.5 | 0.8 | ||
| R MATE/dif | – | 153 ± 18.1 | 213 ± 25.5 | 325 ± 39.2 | 814 ± 111 |
| k a (/hour) | – | 0.21 ± 0.013 | 0.21 ± 0.013 | 0.21 ± 0.013 | 0.21 ± 0.013 |
| k trans (/hour) | – | 2.4 ± 0.36 | 2.4 ± 0.36 | 2.4 ± 0.36 | 2.4 ± 0.36 |
| AUC0–24 (mg•h/L) | 21.4 ± 3.18 | 20.1 | 20.1 | 20.2 | 20.2 |
| CLr (L/hour) | 23.0 ± 3.87 | 29.8 | 29.8 | 30 | 30 |
| 250 mg metformin | |||||
|---|---|---|---|---|---|
| Observed16 | βkidney | ||||
| 0.1 | 0.3 | 0.5 | 0.8 | ||
| RMATE/dif | – | 183 ± 30.1 | 261 ± 43.3 | 402 ± 66.3 | 1,143 ± 186 |
| k a (/hour) | – | 0.21 | 0.21 | 0.21 | 0.21 |
| k trans (/hour) | – | 0.61 ± 0.044 | 0.61 ± 0.044 | 0.61 ± 0.044 | 0.61 ± 0.044 |
| AUC0–12 (mg•hour/L) | 3.75 ± 1.43 | 4.12 | 4.12 | 4.12 | 4.12 |
| CLr (L/hour) | 31.6 ± 9.90 | 28.5 | 28.6 | 28.6 | 28.6 |
| Cmax (μg/L) | 590 ± 240 | 502 | 502 | 502 | 502 |
| Tmax (hour) | 3.3 ± 0.8 | 3.72 | 3.72 | 3.72 | 3.72 |
AUC0–24, area under the curve from 0–24 hours; AUC0–12, area under the curve from 0–12 hours; CLr, renal clearance; Cmax, maximum plasma concentration; Tmax, time of maximum concentration; ka,absorption rate; ktrans, the rate from transit compartment to intestine compartment; RMATE/dif, the ratio of the intrinsic clearance of MATEs to the intrinsic passive diffusion clearance via efflux out of cells to the urinary lumen.