Summary of biotransformation products in plasma from whole blood incubation, liver (L) fraction incubation, and time-proportionally pooled plasma obtained after a single i.v. administration of [14C]AMG 416 to normal and bilaterally nephrectomized (BN) male Sprague-Dawley rats
| Component | % 14C-Chromatograma | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| In Vitro | ||||||||||
| Plasma | Liver S9 | Kidney S9 | Hepatocytes | In Vivo Rat Plasma | ||||||
| Rat | Human | Rat | Human | Rat | Human | Rat | Human | Normal Kidney | BN | |
| AMG 416 | 11.7 | 14.1 | 16.3 | 72.7 | 75.4 | 45.3 | 12.9 | 35.1 | 34.5 | 24.3 |
| M1 | 5.6 | 1.4 | ND | ND | L | ND | L | L | 4.3 | 17.8 |
| M5 | ND | ND | ND | 3.5 | 2.2 | 1.7 | ND | 1.4 | ND | ND |
| M9 | ND | ND | ND | 9.4 | ND | 3.8 | ND | ND | ND | ND |
| M10 | 14.2 | 1.1 | 74.0 | ND | 3.8 | ND | 68.9 | 30.3 | 10.8 | 19.9 |
| M11 | 2.3 | 1.2 | ND | 3.6 | ND | 20.7 | ND | ND | 2.0 | 5.8 |
| M12 | 1.6 | 1.7 | 1.2 | ND | 3.8 | 3.8 | 15.8 | 26.1 | 2.3 | 4.7 |
| M13 | 1.4 | 3.9 | ND | ND | ND | ND | ND | 2.6 | ND | 2.0b |
| M14 | 1.9c | ND | 3.2 | 6.6 | ND | 3.1 | ND | 0.5 | 0.5 | 0.6 |
| M15 | 1.5 | 1.5 | ND | ND | ND | ND | ND | 2.9 | 2.5b | 2.9b |
| M16 | ND | ND | ND | ND | ND | ND | 2.4 | 1.1 | ND | ND |
| M22 | ND | ND | ND | ND | ND | 1.4 | ND | ND | ND | ND |
| M28 | 1.6 | 1.8 | L | L | L | L | L | L | ND | 1.1b |
| Protein conjugate(s) | 58.9 | 71.4 | ND | ND | ND | ND | ND | ND | 42.3 | 18.7 |
| U2 | ND | ND | ND | ND | ND | ND | ND | ND | ND | 2.2 |
| Otherd | 0.8 | 1.9 | 5.3 | 4.1 | 14.8 | 20.3 | ND | ND | ND | ND |
BN, bilaterally nephrectomized; ND, not detected; U2, unknown component.
%14C-chromatogram = 100*cpm counts in the area under the region of interest (ROI)/sum of cpm counts in all ROI.
↵b No mass spectral data were available because the peak intensity was below the detection limit. Identity was based on retention time matches with corresponding peaks observed in the in vitro plasma profile.
↵c M14 and M15 were coeluted.
↵d The sum of all other peaks. In liver and kidney S9 fractions, the highest component was the late eluting putative protein conjugates (not characterized further). Up to nine additional metabolites were detected with each at <1% administered radioactivity.