Table 7. Pharmacokinetic Properties of 8a and 8b in Sprague Dawley Ratsa.
|
8a |
8b |
||||
|---|---|---|---|---|---|
| oralb | ivc | ipd | oralb | ivc | |
| dose (mg/kg) | 20 | 4.5 | 19 | 19 | 1.0 |
| apparent t1/2 (h) | 7.9 | 12 | 9.1 | c.n.c. | 87 |
| % dose in urine | 0.08 | 0.05 | 0.01 | n.d. | n.d. |
| Cmax (μM) | 0.11 | 3.3 | 0.19 | ||
| Tmax (min) | 200 | 15 | 100 | ||
| oral bioavailability F% | 6–7 | 45.7 | 4–5 | ||
| Vdss (L/kg) | 13 | 19 | |||
| plasma clearance (mL/min/kg) | 73 | 22 | |||
a
n.d. = not determined. c.n.c = could not calculate.
b
Oral suspension formulated with aqueous HPMC.
c
iv solution formulated in aqueous vehicle with 40% (v/v) propylene glycol.
d
ip suspension formulated in aqueous vehicle with 10% DMSO.