Table 1.
Plasma PK Parameters of Oral Ziritaxestat, IV 14 C‐Ziritaxestat, and Total Radioactivity Following Oral Administration of 600 mg Ziritaxestat and a 15‐Minute IV Infusion of 100 μg 14 C‐Ziritaxestat (PK Analysis Set)
| PK Parameter, a Unit | Ziritaxestat Oral 600 mg (n = 6) | 14 C‐Ziritaxestat IV Infusion 100 μg 14 C‐Ziritaxestat (n = 6) | Total Radioactivity IV Infusion 100 μg 14 C‐Ziritaxestat (n = 6) |
|---|---|---|---|
| tmax, h | 3.25 (2.00‐4.00) | 0.25 (0.23‐0.25) | 0.25 (0.23‐0.25) |
| Cmax, μg/mL or ng eq/mL b , c | 8.4 (1.7) | 10.2 (1.4) | 7.8 (0.9) |
| AUCt, μg • h/mL or ng eq • h/mL b | 40.0 (13.4) | 12.4 (3.9) | 20.5 (4.7) |
| AUC∞, μg • h/mL or ng eq • h/mL b | 40.0 (13.4) | 13.2 (4.1) | NC d |
| t1/2, h | 7.0 (1.6) | 2.8 (1.4) | 47.8 (25.6) d |
| CL or CL/F, L/h | 16.3 (4.6) | 8.2 (2.2) | … |
| Vd(area), L | … | 29.9 (7.5) | … |
| F AUC∞, % | 51.1 (4.8) | … | … |
| F AUCt, % | 54.4 (5.2) | … | … |
C, carbon‐14; AUC∞, area under the plasma concentration–time curve from time 0 to infinity; AUCt, area under the plasma concentration–time curve from time 0 to time t; CL, total body clearance; Cmax, maximum plasma concentration; eq, equivalent; F, absolute bioavailability; IV, intravenous; NC, not calculated; PK, pharmacokinetic; SD, standard deviation; t1/2, terminal elimination half‐life; tmax, time to reach maximum plasma concentration; Vd(area), volume of distribution following IV route.
Results are expressed as arithmetic mean (SD) except for tmax, which is expressed as median (range).
Microgram units for ziritaxestat parameters after oral dosing, and nanogram units for 14C‐ziritaxestat and total radioactivity parameters.
For IV infusion, Cmax corresponds to the concentration at the end of the infusion.
Terminal slopes for total radioactivity plasma concentration versus time profiles were reliably determined in 5 of 6 subjects; in the remaining subject, the terminal slope could not be reliably determined.