Pharmacokinetic parameters for AZD0837 (prodrug), AR-H069927 (intermediate metabolite), and AR-H067637 (active metabolite) derived from plasma data in pigs after enteral dosing of AZD0837 alone (n = 5) and in conjunction with ketoconazole (n = 6)
Data are mean ± S.D. or median (range) for tmax.
| AZD0837 | + Ketoconazole | Ratioa | |
|---|---|---|---|
| AUC0–6 h (μmol · h/l) | |||
| AZD0837 | 40.4 ± 22.7 | 74.4 ± 39.1 | 1.99 |
| AR-H069927 | 2.1 ± 1.5 | 2.4 ± 1.8 | 1.08 |
| AR-H067637 | 12.5 ± 8.6 | 19.3 ± 11.3 | 1.51 |
| AUC0–6 h (% of the sum of the AUC0–6 h)b | |||
| AZD0837 | 70.2 ± 15.6 | 75.5 ± 13.3 | |
| AR-H069927 | 4.6 ± 3.7 | 2.4 ± 1.6 | |
| AR-H067637 | 25.1 ± 14.1 | 22.1 ± 14.4 | |
| Cmax (μmol/l) | |||
| AZD0837 | 17.8 ± 8.4 | 26.0 ± 9.5 | 1.61 |
| AR-H069927 | 0.7 ± 0.4 | 0.6 ± 0.4c | 0.76 |
| AR-H067637 | 3.8 ± 2.7 | 4.3 ± 2.6c | 1.11 |
| tmax (h) | |||
| AZD0837 | 1.2 (0.9–1.5) | 1.0 (0.5–1.9) | |
| AR-H069927 | 1.5 (0.5–2.5) | 0.5 (0.5–2.9)c | |
| AR-H067637 | 2.2 (1.9–3.2) | 3.2 (2.5–4.0)c | |
| t1/2 (h) | |||
| AZD0837 | 0.7 ± 0.04 | 1.0 ± 0.4 | |
| AR-H069927 | 1.0 ± 0.1 | 1.6 ± 0.4*c | |
| AR-H067637 | 1.2 ± 0.2 | 2.6 ± 1.4*c | |
| EH | |||
| AZD0837 | 0.41 ± 0.20 | 0.33 ± 0.20 | |
| CLH [ml/(min · kg)] | |||
| AZD0837 | 13 ± 6 | 10 ± 6 |
↵* p < 0.05, significantly different from control phase.
↵a The geometric mean ratio between the control measurement and the ketoconazole phase.
↵b The relative AUC0–6 h expressed as a percentage of the summed AUC0–6 h values of AZD0837, AR-H069927, and AR-H067637.
↵c Pig 16 was excluded from the data analysis.