Metabolite IDa | Percentage of Dose | |||||
---|---|---|---|---|---|---|
Ratsb | BDC Ratsb | Dogsb | ||||
Urine | Feces | Urine | Bile | Urine | Feces | |
M1 | N.D. | N.D. | N.D. | 8.6 | N.D. | N.D. |
M2/M37c | 3.5 | 6.9 | 4.2 | 0.9 | 0.4 | 15.6 |
M3/M26d | 4.0 | 8.2 | 6.7 | 4.0 | 1.2 | 16.3 |
M6 | N.D. | N.D. | 0.3 | 7.2 | 2.9 | 4.8 |
M7/M9e | 0.5 | N.D. | 0.5 | 14.2 | 6.5 | N.D. |
M8 | 0.4 | N.D. | 0.6 | 9.8 | 1.4 | N.D. |
M24 | N.D. | N.D. | N.D. | 2.0 | N.D. | N.D. |
M27 | N.D. | N.D. | N.D. | 0.6 | 0.2 | N.D. |
M28 | N.D. | N.D. | N.D. | N.D. | 0.3 | N.D. |
M30 | N.D. | N.D. | N.D. | 2.8 | N.D. | N.D. |
M32 | N.D. | N.D. | N.D. | 2.2 | N.D. | N.D. |
P | 5.0 | 6.8 | 2.3 | 5.2 | 1.0 | 2.3 |
Total | 13.4 | 21.9 | 14.6 | 57.5 | 13.9 | 39.1 |
N.D., not detected by radioactivity.
↵a Structures of metabolites are shown in Figure 5.
↵b The urine and feces samples from rats and dogs were collected from 0 to 168 h after dosing, and the urine and bile from BDC rats were collected from 0 to 24 h after dosing.
↵c Metabolites M2 and M37 are known to coelute on the HPLC and also have similar mass spectrometric characteristics. Both metabolites were detected in incubations of deuterated BMS-690514 with human liver microsomes and are probably coeluting in these excreta samples. The relative contributions of these two metabolites could not be determined.
↵d Metabolites M3 and M26 coeluted on the HPLC but could be differentiated by mass spectrometry in the urine and fecal samples from rats and in the urine and bile samples from BDC rats. M26 was not detected by mass spectrometry in the urine and fecal samples from dogs.
↵e Metabolites M7 and M9 coeluted on the HPLC but could be differentiated by mass spectrometry in the urine samples from rats, BDC rats, and dogs and in the bile from BDC rats.