Table 5 Biotransformation of individual DHF stereoisomers in isolated guinea pig hepatocytes
From: The stereospecificity of flobufen metabolism in isolated guinea pig hepatocytes
Substrate | Incubation time [h] | Apparent actual clearance [h-1 × 10-3] | ||||
|---|---|---|---|---|---|---|
| Â | Â | M-17203 | (2R;4S)-DHF | (2S;4R)-DHF | (2S;4S)-DHF | (2R;4R)-DHF |
|  | 2 | 1.0 ± 0.2 | 218.2 ± 0.5 | 2.6 ± 0.0 | 21.3 ± 0.6 | 1.5 ± 0.4 |
|  | 4 | 1.2 ± 0.1 | 93.7 ± 1.2 | 1.6 ± 0.1 | 19.5 ± 0.5 | 2.3 ± 0.1 |
(2R;4S)-DHF | Â | Â | Â | Â | Â | Â |
|  | 8 | 1.1 ± 0.1 | 24.2 ± 2.0 | 0.8 ± 0.0 | 6.7 ± 0.0 | 0.2 ± 0.0 |
|  | 24 | 3.1 ± 0.1 | 6.9 ± 1.4 | 0.2 ± 0.0 | 3.0 ± 0.4 | 0.1 ± 0.0 |
|  | 2 | 1.7 ± 0.0 | 16.7 ± 0.4 | 115.6 ± 1.8 | 36.8 ± 1.3 | 1.8 ± 0.3 |
|  | 4 | 1.9 ± 0.1 | 20.1 ± 0.4 | 47.1 ± 1.1 | 34.7 ± 0.4 | 1.4 ± 0.3 |
(2S;4R)-DHF | Â | Â | Â | Â | Â | Â |
|  | 8 | 1.7 ± 0.0 | 9.6 ± 0.1 | 7.7 ± 0.5 | 14.3 ± 0.1 | 0.1 ± 0.0 |
|  | 24 | 3.2 ± 0.2 | 2.1 ± 0.6 | 1.2 ± 0.5 | 6.0 ± 0.5 | — |
|  | 2 | 2.1 ± 0.2 | 35.1 ± 1.7 | 5.2 ± 0.4 | 179.2 ± 6.0 | — |
|  | 4 | 2.1 ± 0.0 | 26.2 ± 0.3 | 4.3 ± 0.0 | 54.8 ± 1.2 | 0.2 ± 0.0 |
(2S;4S)-DHF | Â | Â | Â | Â | Â | Â |
|  | 8 | 1.3 ± 0.1 | 9.0 ± 0.5 | 2.1 ± 0.3 | 12.7 ± 0.8 | — |
|  | 24 | 3.8 ± 0.1 | 2.2 ± 0.5 | 0.1 ± 0.0 | 5.0 ± 0.6 | — |
|  | 2 | — | 122.4 ± 3.5 | 19.6 ± 0.5 | 12.3 ± 0.3 | 84.6 ± 6.4 |
|  | 4 | 0.8 ± 0.0 | 71.6 ± 1.6 | 11.7 ± 0.4 | 15.1 ± 0.1 | 8.0 ± 0.7 |
(2R;4R)-DHF | Â | Â | Â | Â | Â | Â |
|  | 8 | 1.4 ± 0.1 | 21.5 ± 1.3 | 2.2 ± 0.1 | 8.2 ± 0.3 | 0.4 ± 0.0 |
|  | 24 | 3.3 ± 0.3 | 3.8 ± 0.3 | 0.3 ± 0.0 | 2.7 ± 0.1 | — |