Table 6.
In Vivo PK Data for Analogue 33 Following IV and PO Administration in Ratsa
| route | dose (µmol/kg) | C0b (µM) | CLc (mL/h/kg) | t1/2d (h) | Vsse (mL/kg) | AUClastf (µM·h) | AUCINFg (µM·h) | %Fi |
|---|---|---|---|---|---|---|---|---|
| IV | 5.1 | 58.6 (1.8) | 5.06 (0.49) | 22.0 (3.0) | 156 (9.0) | 795 (48) | 1017 (93) | NA |
| route | dose (µmol/kg) | Cmaxh (µM) | Tmaxh (h) | t1/2d (h) | Vsse (mL/kg) | AUClastf (µM·h) | AUCINFg (µM·h) | %Fi |
| PO | 12.7 | 62.2 (4.3) | 2.67 (1.15) | 38.8 (17.3) | NA | 2011 (326) | 3636 (1588) | 143 (62.4) |
Data are represented as the mean with standard deviation in parentheses (mean (SD)). Dosing groups consisted of three drug naïve adult male Sprague–Dawley rats. IV administration: the test article was administered at the 5.1 µmol/kg (2 mg/kg) dose; test article vehicle = 3% DMA/45% PEG300/12% EtOH/40% sterile H2O; PO administration, test article was administered at the 12.7 µmol/kg (5 mg/kg) dose; vehicle = 2% Tween 80 in 0.9% saline. Bioavailability; F = (AUCINFpo × doseiv) ÷ AUCINFiv × dosepo).
Observed initial concentration of compound in plasma at time zero.
Total body clearance.
Apparent half-life of the terminal phase of elimination of the compound from plasma.
Volume of distribution at steady state.
Area under the plasma concentration versus time curve from 0 to the last time point that the compound was quantifiable in plasma.
Area under the plasma concentration versus time curve from 0 to infinity.
Maximum observed concentration of the compound in plasma.
Time of maximum observed concentration of the compound in plasma.