Table 4.
Plasma concentration–time data for difelikefalin and metabolites (pooled samples by time point)
| Healthy subjects | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Time (h) | |||||||||||||
| Analyte | 0.0 | 0.083 | 0.25 | 0.5 | 1 | 2 | 4 | 6a | 8a | 12a | 24a | 36a | 48a |
| Difelikefalin | 0.00 | 23.8 | 16.9 | 12.6 | 9.17 | 6.01 | 3.22 | ||||||
| MP1 | 0.00 | 0.356 | 0.269 | 0.351 | b | b | b | ||||||
| MP2 | 0.00 | 0.166 | b | b | b | b | b | ||||||
| MP3 | 0.00 | 0.282 | b | b | b | b | b | ||||||
| MP4 | 0.00 | 0.141 | b | b | b | b | b | ||||||
| Total | 0.00 | 24.7 | 17.2 | 13.0 | 9.17 | 6.01 | 3.22 | ||||||
| Subjects on hemodialysis | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Time (h) | |||||||||||||
| Analyte | 0.0 | 0.083 | 0.25 | 0.5 | 1 | 2 | 4 | 6 | 8 | 12 | 24 | 36 | 48 |
| Difelikefalin | 0.00 | 24.7 | 16.6 | 14.2 | 11.8 | 10.8 | 9.33 | 8.46 | 7.81 | 6.99 | 5.22 | 4.17 | 3.06 |
| MP1 | 0.00 | 0.548 | 0.344 | 0.242 | 0.159 | b | b | b | b | b | b | b | b |
| MP2 | 0.00 | b | b | b | b | b | b | b | b | b | b | b | b |
| MP3 | 0.00 | 0.340 | 0.249 | b | b | b | b | b | b | b | b | b | b |
| MP4 | 0.00 | b | b | b | b | b | b | b | b | b | b | b | b |
| Total | 0.00 | 25.6 | 17.2 | 14.4 | 12.0 | 10.8 | 9.33 | 8.46 | 7.81 | 6.99 | 5.22 | 4.17 | 3.06 |
Concentrations reported in ng-eq/mL. Concentrations at pre-dose (0 h) were not determined; these were set to 0.00 ng-eq/mL during subsequent calculations
LC-RAD liquid-chromatography radiochromatogram
aTime point not included in metabolic profiling; in healthy subjects, samples from 0–4 h contained 98% of the plasma radioactivity
bCharacterization of some peaks in LC–RAD spectra (MP1, MP2, MP3, and MP4, found at less than 0.6 ng-eq/mL at any given time point) were not undertaken due to their low relative peak area