Table 2.
Pharmacokinetic characteristics of flupirtine after intravenous infusion and chronic administration of flupirtine MR in rapid metabolizers (GST+) and poor metabolizers (GST-) of the glutathione-S-transferase P1
| 100 mg intravenously | 400 mg orally, multiple dose | ||||
|---|---|---|---|---|---|
| GST+ (n = 24) | GST- (n = 12) | GST+ (n = 24) | GST- (n = 12) | ||
| AUC/AUC(0–24 h) (FPT) | (μg ml−1 h) | 10.5 ± 4.12 | 10.2 ± 4.19 | 22.5 ± 6.59 | 18.3 ± 7.79* |
| AUC/AUC(0–24 h) (D13223) | (μg ml−1 h) | 7.37 ± 2.42 | 7.61 ± 5.37 | 15.9 ± 4.35 | 15.1 ± 8.87 |
| F | (%) | – | – | 58.3 ± 22.6 | 45.7 ± 11.8 |
| t1/2 | (h) | 9.00 ± 1.29 | 8.61 ± 1.26 | 27.1 ± 25.0 | 21.1 ± 10.5 |
| CLR | (ml min−1) | 13.7 ± 7.89 | 13.2 ± 7.11 | 12.6 ± 7.63 | 14.4 ± 9.06 |
| Aeurine, FLU free | (mg) | 7.72 ± 3.77 | 7.03 ± 2.89 | 16.5 ± 10.3 | 14.0 ± 8.06 |
| Aeurine, D13223 free | (mg) | 6.48 ± 2.22 | 6.94 ± 2.63 | 14.8 ± 6.81 | 12.8 ± 7.49 |
| Aeurine, MERC | (mg) | 10.6 ± 2.84 | 11.3 ± 3.29 | 21.8 ± 6.77 | 22.4 ± 6.74 |
| Aefaeces, FLU free | (mg) | 0.249 ± 0.187 | 0.468 ± 0.374* | 26.7 ± 14.8 | 38.6 ± 18.2* |
| Aefaeces, D13223 free | (mg) | 0.078 ± 0.059 | 0.119 ± 0.068* | 0.381 ± 0.193 | 0.463 ± 0.252 |
| Aeall/Doseurine+faeces | (%) | 25.1 ± 6.32 | 25.9 ± 6.67 | 20.1 ± 5.57 | 22.1 ± 5.62 |
*P < 0.05 compared with GST+ (Mann–Whitney); n.d. = not determined; MR = modified release.