Pharmacokinetic parameters of edaravone, edaravone sulfate, and edaravone glucuronide in Mrp4 knockout and wild-type mice
Edaravone was infused i.v. for 120 min. Each value was determined from the data shown in Figure 5 and the equations described under Materials and Methods. Each value represents the mean ± S.E. (n = 10-11).
Wild-type | Mrp4−/− | |
|---|---|---|
| CLCRE (ml/min/kg) | 8.63 ± 1.50 | 8.91 ± 1.65 |
| CLtotal (ml/min/kg) | ||
| Edaravone | 105 ± 5 | 104 ± 8 |
| CLrenal, p | ||
| Edaravone (ml/min/kg) | 0.915 ± 0.114 | 0.818 ± 0.129 |
| Sulfate | 7.33 ± 0.43 | 8.98 ± 1.17 |
| Glucuronide | 22.1 ± 1.8 | 19.6 ± 2.7 |
| CLrenal, k | ||
| Sulfate (ml/min/kg) | 4.92 ± 0.83 | 2.86 ± 0.53 |
| Glucuronide | 5.06 ± 1.18 | 2.01 ± 0.45* |
| Ckidney | ||
| Edaravone (nmol/g kidney) | 7.79 ± 2.16 | 14.1 ± 2.7 |
| Sulfate | 32.8 ± 13.8 | 53.7 ± 15.4 |
| Glucuronide | 24.8 ± 11.2 | 65.7 ± 26.9 |
| Kp, kidney | ||
| Edaravone | 3.39 ± 1.08 | 6.82 ± 1.73 |
| Sulfate | 2.72 ± 1.19 | 7.58 ± 3.44 |
| Glucuronide | 5.47 ± 2.40 | 15.0 ± 6.0 |
| Urinary recovery | ||
| Edaravone (% dose) | 0.781 ± 0.057 | 0.730 ± 0.069 |
| Sulfate | 31.9 ± 1.9 | 26.6 ± 2.9 |
| Glucuronide | 26.9 ± 1.7 | 26.6 ± 3.2 |
↵* P < 0.05, significantly different from wild-type mice using Student's t-test.