Pharmacokinetic parameters of metformin in control and PYR-treated mice
Each value was determined from the data shown in Fig. 5 and the equations described under Materials and Methods. Each value represents the mean ± S.E. (n = 3–4).
| Parameter | PYR Dose, Urinary Bladder Cannulated Mice | PYR Dose, Bile Duct Cannulated Mice | ||
|---|---|---|---|---|
| 0 | 2 | 0 | 2 | |
| μmol/kg | ||||
| Cp,ss (μM) | 3.47 ± 0.15 | 3.65 ± 0.17 | 6.18 ± 0.58 | 6.64 ± 1.06 |
| Ckidney (nmol/g kidney) | 15.1 ± 1.3 | 55.8 ± 8.5* | 41.1 ± 3.5 | 89.6 ± 12.4** |
| Cliver (nmol/g liver) | 5.33 ± 0.81 | 21.5 ± 2.4** | 12.4 ± 1.2 | 32.5 ± 6.0* |
| Vurine (nmol/min/kg) | 190 ± 5 | 203 ± 7 | N.D. | N.D. |
| Furine (%) | 95 ± 3 | 101 ± 4 | N.D. | N.D. |
| Vbile (nmol/min/kg) | N.D. | N.D. | 0.306 ± 0.057 | 0.336 ± 0.048 |
| Fbile (%) | N.D. | N.D. | 0.15 ± 0.03 | 0.17 ± 0.02 |
| CLtot,plasma (ml/min/kg) | 57 ± 2 | 56 ± 3 | 33 ± 3 | 34 ± 8 |
| CLrenal, plasma (ml/min/kg) | 55 ± 1 | 55 ± 1 | N.D. | N.D. |
| CLrenal, kidney (ml/min/kg) | 9.6 ± 1.1 | 3.4 ± 0.7** | N.D. | N.D. |
| CLbile, plasma (ml/min/kg) | N.D. | N.D. | 0.050 ± 0.010 | 0.051 ± 0.003 |
| CLbile, liver (ml/min/kg) | N.D. | N.D. | 0.026 ± 0.003 | 0.012 ± 0.002** |
| GFR (ml/min/kg) | 15 ± 2 | 12 ± 1 | N.D. | N.D. |
| Kp,kidney (ml/g kidney) | 4.3 ± 0.5 | 15 ± 2** | 6.3 ± 0.1 | 13 ± 3 |
| Kp,liver (ml/g liver) | 1.5 ± 0.3 | 5.7 ± 0.5** | 1.9 ± 0.2 | 4.5 ± 0.5** |
Ckidney, drug concentration in the kidney at 120 min; Cliver, drug concentration in the liver at 120 min; Vbile, biliary excretion rate; Fbile, fractional biliary excretion ratio; CLbile, plasma, hepatic clearance with respect to the concentration in circulating plasma; CLbile, liver, hepatic clearance with respect to the liver concentration; N.D., not determined.
↵* p < 0.05.
↵** p < 0.01.