Comparison between the pharmacokinetic parameters describing elimination via the bile route for AZD0837 (prodrug), AR-H069927 (intermediate metabolite), and AR-H067637 (active metabolite) after enteral administration of AZD0837 (n = 5) and intravenous dosing of AZD0837 (n = 2) and AR-H067637 (n = 2)
| AZD0837 (enteral)a | AZD0837 (i.v.)b | AR-H067637 (i.v.)b | |
|---|---|---|---|
| t½, plasma (h) | |||
| AZD0837 | 0.7 | 0.7, 0.7 | N.A. |
| AR-H069927 | 1.0 | 0.7, 0.8 | N.A. |
| AR-H067637 | 1.2 | 1.0, 1.2 | 1.0, 1.1 |
| Aebile (% of dose) | |||
| AZD0837 | 0.3 | 0.2, 0.3 | N.A. |
| AR-H069927 | 0.2 | 0.1, 0.2 | N.A. |
| AR-H067637 | 53.0 | 67.5, 72.1 | 61.2, 65.8 |
| Aeintestine (% of dose)c | |||
| AZD0837 | 2.6 | 0.9, 0.7 | N.A. |
| AR-H069927 | 0.5 | 0.4, 0.3 | N.A. |
| AR-H067637 | 1.0 | 0.3, 0.3 | 0.1, 0.6 |
| CLbile [ml/(min · kg)] | |||
| AZD0837 | 0.04 | 0.04, 0.05 | N.A. |
| AR-H069927 | 0.49 | 0.52, 0.80 | N.A. |
| AR-H067637 | 33.9 | 23.5, 70.3 | 14.1, 23.6 |
| CLintestine [ml/(min · kg)]c | |||
| AZD0837 | 0.4 | 0.13, 0.15 | N.A. |
| AR-H069927 | 2.8 | 1.45, 1.83 | N.A. |
| AR-H067637 | 1.1 | 0.12, 0.40 | 0.05, 0.14 |
N.A., not available.
↵a Data displayed as mean values (n = 5 and n = 3 for Aeintestine and CLintestine).
↵b Data displayed for each animal (n = 2).
↵c These values were scaled by a factor of 50 to approximate the secretion into the entire small intestine from the 10-cm long jejunal segment (see Results).