Exposures (AUC) of brivanib and metabolites in plasma from rats, monkeys, and humans after oral administration of [14C]brivanib alaninate
| Metabolite Identification | Brivanib and Metabolite AUC in Plasmaa | |||||
|---|---|---|---|---|---|---|
| Rat Plasmab | Monkey Plasmac | Human Plasmad | ||||
| AUC0–6 he | % to AUC of TRA | AUC0–12 h | % to AUC of TRA | AUC0–12 h | % to AUC of TRA | |
| μg BMS-540215 Eq/l · h | ||||||
| TRA | 139,766.0 | 69,315.0 | 65,627.4 | |||
| Brivanibf | 23,709.8 | 17.0 | 42,587.2 | 61.4 | 30,257.7 | 46.1 |
| M6 | 37,494.4 | 26.8 | 5622.3 | 8.1 | 3835.4 | 5.8 |
| M19 | 5443.1 | 3.9 | 3272.2 | 4.7 | 1202.5 | 1.8 |
| M25 | 1628.2 | 1.2 | 755.8g | 1.1 | 3611.4 | 5.5 |
| M26 | 12,825.3 | 9.2 | 5006.0h | 7.2 | 4119.3 | 6.3 |
| M32 | 29,545.4 | 21.1 | 4597.3 | 6.6 | 9668.9 | 14.7 |
↵a Concentrations of brivanib and metabolites were estimated on the basis of their percentage of radioactivity from plasma radioprofiles and plasma TRA. AUC was calculated by noncompartmental methods with Kinetica software.
↵b Rats were administered a single oral dose of 100 mg/kg brivanib alaninate.
↵c Monkeys were administered a single oral dose of 10 mg/kg brivanib alaninate.
↵d Humans were administered a single oral dose of 800 mg of brivanib alaninate.
↵e Rat plasma at 12 h was not profiled because of low radioactivity and limited plasma volumes. Therefore, AUC from 0 to 6 h was determined for brivanib and metabolites in rat plasma.
↵f Brivanib is reported as a total of brivanib and its enantiomer.
↵g Calculated on the basis of the concentration of M25 in plasma at 1, 2, and 4 h time points (AUC0–4 h).
↵h Metabolite M26 coelutes with M28 on HPLC. However, based on the MS analysis, the radioactive peak was mainly attributed to M26.