Pharmacokinetic parameters of edaravone, edaravone sulfate, and edaravone glucuronide in Bcrp knockout and wild-type mice
Edaravone was infused i.v. for 120 min. Each value was determined from the data shown in Figure 4 and the equations described under Materials and Methods. Each value represents the mean ± S.E. (n = 6).
Wild-type | Bcrp-/- | |
|---|---|---|
| CLCRE (ml/min/kg) | 10.9 ± 1.5 | 9.91 ± 2.76 |
| CLtotal (ml/min/kg) | ||
| Edaravone | 108 ± 3 | 111 ± 7 |
| CLrenal, p (ml/min/kg) | ||
| Edaravone | 0.963 ± 0.190 | 0.803 ± 0.229 |
| Sulfate | 10.5 ± 0.7 | 5.78 ± 0.51** |
| Glucuronide | 25.2 ± 2.7 | 18.2 ± 1.8 |
| CLrenal, k (ml/min/kg) | ||
| Sulfate | 4.85 ± 0.33 | 3.62 ± 0.41* |
| Glucuronide | 4.66 ± 0.41 | 3.66 ± 0.56 |
| Ckidney (nmol/g kidney) | ||
| Edaravone | 4.86 ± 0.59 | 4.29 ± 0.69 |
| Sulfate | 13.6 ± 1.2 | 13.8 ± 2.7 |
| Glucuronide | 13.3 ± 1.9 | 15.4 ± 2.5 |
| Kp, kidney | ||
| Edaravone | 2.85 ± 0.41 | 4.46 ± 1.92 |
| Sulfate | 2.23 ± 0.19 | 2.03 ± 0.22 |
| Glucuronide | 3.99 ± 0.55 | 4.04 ± 0.43 |
| Urinary recovery (% dose) | ||
| Edaravone | 0.871 ± 0.076 | 0.619 ± 0.120 |
| Sulfate | 28.9 ± 3.1 | 19.9 ± 2.1* |
| Glucuronide | 37.0 ± 0.8 | 37.3 ± 3.7 |