Table 3.
Summary of pharmacokinetic properties (mean ± SEM) after a single IV or gavage dose (three dose levels) of PFHxSK in male and female Hsd:Sprague Dawley Rats.
| Male |
Female |
|||||||
|---|---|---|---|---|---|---|---|---|
| Dose (mg/kg) | 4 (IV)a | 4b | 16 b | 32 b | 4 (IV) a | 4 b | 16 b | 32 b |
| Cmaxc (mM) | 0.11 ± 0.01 | 0.08 ± 0.01 | 0.29 ± 0.02 | 0.41 ± 0.04 | 0.15 ± 0.03 | 0.06 ± 0.01 | 0.21 ± 0.02 | 0.30 ± 0.02 |
| Tmaxc (hr) | n/a | 6.90 ± 1.26 | 5.89 ± 0.82 | 5.28 ± 0.99 | n/a | 2.81 ± 0.38 | 2.24 ± 0.48 | 1.87 ± 0.43 |
| k10 T1/2 (days) | 13.0 ± 1.5 | 17.6 ± 1.8 | 16.5 ± 1.1 | 14.8 ± 1.2 | 0.70 ± 0.08 | 2.33 ± 0.07 | 2.19 ± 0.06 | 1.98 ± 0.05 |
| α T1/2 (hr) | 13.0 ± 3.8 | n/a | n/a | n/a | 0.70 ± 0.31 | n/a | n/a | n/a |
| β T1/2 (days) | 33.8 ± 6.4 | n/a | n/a | n/a | 1.56 ± 0.04 | n/a | n/a | n/a |
| AUCc (μM*hr) | 50.74 ± 4.97 | 49.74 ± 4.00 | 167.0 ± 9.5 | 212.7 ± 15.0 | 3.65 ± 0.17 | 5.20 ± 0.22 | 16.30 ± 1.02 | 20.84 ± 1.30 |
| AUCc / Dose (μM *hr/mg/kg) | 12.7 ± 1.4 | 12.4 ± 1.0 | 10.4 ± 0.6 | 6.65 ± 0.47 | 0.912 ± 0.044 | 1.30 ± 0.06 | 1.02 ± 0.06 | 0.651 ± 0.041 |
| CL (mL/hr/kg) | 0.197 ± 0.019 | 0.201 ± 0.016 | 0.239 ± 0.014 | 0.376 ± 0.027 | 2.73 ± 0.13 | 1.92 ± 0.09 | 2.46 ± 0.15 | 3.84 ± 0.24 |
| V1d (mL/kg) | 88.4 ± 5.1 | 123 ± 11 | 137 ± 9 | 192 ± 17 | 66.3 ± 7.6 | 155 ± 9 | 186 ± 14 | 264 ± 20 |
| V2e (mL/kg) | 136 ± 27 | n/a | n/a | n/a | 77.6 ± 10.8 | n/a | n/a | n/a |
| Ff (%) | n/a | 98 | 82 | 52 | n/a | 142 | 112 | 71 |
n/a: not applicable.
CL=clearance.
F=bioavailability.
T1/2=half-life.
aTwo-compartment model.
bOne-compartment model.
c Predicted from model.
dVolume of distribution for the central compartment.
eVolume of distribution for the peripheral compartment.
f Estimated by dividing dose-adjusted IV AUC by dose-adjusted Gavage AUC.