TABLE 3.
Summary of plasma pharmacokinetics parameters
| Parameter | 14C‐napabucasin 240 mg | |||
|---|---|---|---|---|
| Napabucasin in plasma | M1 in plasma | Plasma TRA | Whole blood TRA | |
| Cmax (ng/ml or ng eq/g) | 444 (127) | 378 (147) | 664 (398) | 344 (196) |
| Tmax (h) a | 2.75 (1.00–8.00) | 2.25 (1.50–10.00) | 10.00 (4.00–12.00) | 9.00 (6.00–10.00) |
| tlag (h) a | 0.00 | 0.00 | 1.25 (0–4.00) | 4.00 (3.00–6.00) |
| AUClast (h*ng/ml or h*ng eq/g) | 4020 (1190) | 3050 (1300) | 7770 (6610) | 3760 (2780) |
| AUCinf (h*ng/ml or h*ng eq/g) | 4200 (1180) | 3160 (1300) | NC b | NC d |
| t1/2 (h) | 7.92 (3.07) | 7.14 (3.18) | 11.8 (3.46) c | NC d |
| Vz/F (L) | 685 (282) | — | NC b | NC d |
| CL/F (L/h) | 61.3 (15.1) | — | NC b | NC d |
| M/P‐AUClast | NA | 0.753 (0.184) | — | — |
| M/P‐AUCinf | NA | 0.744 (0.170) | — | — |
| M/P‐Cmax | NA | 0.844 (0.244) | — | — |
| R‐AUClast | 0.778 (0.529) | 0.594 (0.461) | — | — |
| R‐AUCinf | 0.464 (0.227) | 0.382 (0.153) | — | — |
| R‐Cmax | 0.972 (0.744) | 0.844 (0.662) | — | — |
Data are reported for N = 8. Arithmetic mean (SD) data are presented, except for Tmax and tlag.
TRA could represent labeled napabucasin, labeled M1, or other labeled napabucasin metabolites, which could vary over time, especially at late time points.
Abbreviations: AUC, area under the curve; AUCinf, AUC from time 0 to infinity; AUClast, AUC from time 0 to time of last measurable concentration; CL/F, apparent systemic clearance; Cmax, peak concentration observed; CV, coefficient of variation; eq, equivalent; M/P‐AUC, metabolite to parent AUC ratio; M/P‐Cmax, metabolite to parent Cmax ratio; NA, not applicable; NC, not calculated; R‐AUC, ratio of analyte to TRA based on AUC; R‐Cmax, ratio of analyte to TRA based on Cmax; SD, standard deviation; t1/2, apparent terminal elimination half‐life; tlag, time prior to first quantifiable concentration; Tmax, time to peak concentration; TRA, total radioactivity; Vz/F, apparent volume of distribution.
Median (range) data are presented.
It was not possible to calculate the full summary statistics because a t1/2 estimate was not always possible (see footnote c) and was more than 30% extrapolated for 2 of 4 subjects.
Half‐life estimates were possible for 4 subjects, but for 3 subjects the estimates were determined over a period <2 half‐lives.
Terminal phase could not be defined for any profile in whole blood, so only observed parameters were calculable.