Table 2.
Pharmacokinetic Parameters for Intravenously Injected Microdoses of 11C-Labeled Drugs in Rhesus Monkeys
| Drug | Dose (mg/kg) | Cmax, %ID brain (%ID) | Cmax, SUV brain (SUV) | Tmax brain (min) | f u(plasma) | f u(brain) | V u(brain) | AUCbrain 0-90min/AUCplasma 0-90min (K P) | f u(brain)AUCbrain 0-90min/f u(plasma) AUCplasma 0-90min (K P u,u) | AUCbrain 0-90min/f u(plasma) V u(brain) AUCplasma 0-90min (K P u,u) |
|---|---|---|---|---|---|---|---|---|---|---|
| [11C]Caffeine | micro | 2.8 | 3.0 | 1.8 | 0.96a | 0.52b | 1.92c | 0.75 | 0.4 | 0.4 |
| 2.5 | 2.8 | 2.9 | 1.8 | 0.96 a | 0.76 | 0.4 | 0.4 | |||
| [11C]Citalopram | micro | 2.2 | 2.0 | 48 | 0.49 | 0.03b | 60d | 11.7 | 0.7 | 0.4 |
| 3 | 3.3 | 3.0 | 28.5 | 0.52 | 11.7 | 0.7 | 0.4 | |||
| [11C] Clomipramine | micro | 3.8 | 3.4 | 42 | 0.01 | 0.006e | 863d | 20.1 | 12.1 | 2.3 |
| 0.8 | 6.2 | 5.5 | 22.5 | 0.01 | 20.7 | 12.4 | 2.4 | |||
| [11C]Clozapine | micro | 5.3 | 3.5 | 66 | 0.09 | 0.009b | 220c | 11.9 | 1.2 | 0.6 |
| 1.5 | 5.2 | 3.4 | 19.5 | 0.11 | 9.6 | 0.8 | 0.4 | |||
| [11C]Diazepam | micro | 3.4 | 3.9 | 1.8 | 0.16 | 0.05b | 20f | 2.0 | 0.6 | 0.6 |
| 2 | 3.4 | 3.9 | 1.8 | 0.12 | 1.7 | 0.7 | 0.7 | |||
| [11C]Doxepin | micro | 4.6 | 4.8 | 48 | 0.14 | 0.025g | 115c | 25.5 | 4.5 | 1.6 |
| 0.1 | 4.1 | 4.3 | 19.5 | 0.14 | 20.9 | 3.7 | 1.3 | |||
| [11C]Morphine | micro | 0.11 | 0.070 | 84 | 0.76 | 0.5b | 3.7f | 0.36 | 0.2 | 0.1 |
| 0.5 | 0.089 | 0.063 | 66 | 0.69 | 0.19 | 0.1 | 0.1 | |||
| [11C]Nicotine | micro | 5.9 | 4.2 | 3.5 | 0.96 | 1h | 2.6c | 5.5 | 5.7 | 2.2 |
| 0.12 | 5.5 | 3.9 | 4.5 | 0.99 | 6.3 | 6.6 | 2.4 | |||
| [11C]Selegiline | micro | 3.3 | 3.4 | 4.5 | 0.14 | 0.056b | 38.56c | 11.2 | 4.5 | 2.1 |
| 0.5 | 4.1 | 4.3 | 2.5 | 0.18 | 5.9 | 1.8 | 0.9 | |||
| [11C]Sertraline | micro | 4.4 | 5.0 | 84 | 0.01 | 0.00066b | 4184d | 24.6 | 1.6 | 0.6 |
| 1 | 4.5 | 5.1 | 78 | 0.02 | 25.5 | 0.8 | 0.3 | |||
| [11C]Sulpiride | micro | 0.0086 | 0.0075 | 90 | 0.93 | 0.63b | 4.58c | 0.0029 | 0.001 | 0.0 |
| 2 | 0.0099 | 0.0086 | 78 | 0.96 | 0.0022 | 0.001 | 0.0 | |||
| [11C]Venlafaxine | micro | 3.6 | 2.3 | 16.5 | 0.92 | 0.21b | 10c | 8.0 | 1.5 | 0.9 |
| 2 | 4.0 | 2.6 | 13.5 | 0.93 | 8.3 | 1.5 | 0.9 | |||
| [11C]Verapamil | micro | 1.3 | 1.1 | 5.5 | 0.25 | 0.03i | 54d | 3.2 | 0.4 | 0.2 |
| 0.3 | 1.9 | 1.7 | 5.5 | 0.28 | 2.7 | 0.3 | 0.2 |
The unbound fraction in plasma was determined using ultrafiltration on the day of the experiment, whereas the unbound fraction in brain obtained from homogenate (f u.brain) or brain slice (V u.brain) incubations was obtained from the literature. For the drugs for which V u.brain was not reported in the literature, the pH partition model described by Friden et al. was used to calculate V u.brain from f u.brain.
aThe unbound fraction in rhesus plasma could not be determined, instead the corresponding free fraction from cynomolgus monkey was used.
bMaurer et al., 2005.
cCalculated using the pH partition model.
dFriden et al., 2011.
eDi et al., 2011.
fFriden et al., 2014.
gSummerfield et al., 2007.
hRollema et al., 2010.
iKalvass et al., 2007.