Table 5.
In vitro metabolism and pharmacokinetic properties of 8 in mice.[a]
| Solubility in PBS (μM) | 139 ± 1 |
| Plasma t1/2 (min) | >120[b] |
| MLM (NADPH) t1/2 (min) | >60[c] |
| MLM (UDPG) t1/2 (min) | >60[d] |
| 3 mg/kg, i.v | 3 mg/kg, p.o. | |
|---|---|---|
| Cmax (ng/mL) | 1660±166 | 613±68 |
| Tmax (min) | (5.0) | 30 |
| Cl (mL/min/Kg) | 33.2±1.6 | 49±8 |
| t1/2 (min) | 73.9±3.7 | 104±16 |
| Vd (L/Kg) | 3.5±0.2 | 7.4±1.1 |
| AUCplasma (h × ng/mL) | 1366.8±68.3 | 988±157 |
| AUCbrain (h × ng/mL) | 404.3±109.1 | 181±28 |
| F (%) | - | 72±11 |
[a]
NADPH, reduced nicotinamide adenine dinucleotide phosphate; PBS, phosphate-buffered saline; t1/2, terminal half life; UDPG, uridine diphosphate glucose; AUC, area under the curve; Cmax, maximal plasma concentration; F%, oral bioavailability; Tmax, time at which Cmax is reached.
[b]
83± 4% remaining at 120 min;
[c]
70± 7% remaining at 60 min;
[d]
96% remaining at 60 min.