Table 2. Kinetic rate constants estimated with a 2-TCMi at baseline and after PF-04457845 with 60 minutes of scan data.
| 60 minutes | K1 (mL/cm3/min) | k2 (1/min) | k3 (1/min) | Ki (mL/cm3/min) | λk3 (mL/cm3/min) |
|---|---|---|---|---|---|
| Prefrontal cortex | |||||
| Baseline | 0.28 (0.03) | 0.11 (0.02) | 0.061 (0.009) | 0.102 (0.010) | 0.159 (0.015) |
| PF 1 mg | 0.35 (0.02) | 0.12 (0.01) | 0.007 (0.002) | 0.018 (0.004) | 0.019 (0.005) |
| PF 4 mg | 0.31 (0.02) | 0.10 (0.01) | 0.003 (0.001) | 0.010 (0.002) | 0.010 (0.003) |
| PF 20 mg | 0.30 (0.06) | 0.10 (0.01) | 0.006 (0.001) | 0.015 (0.001) | 0.016 (0.001) |
| Temporal cortex | |||||
| Baseline | 0.29 (0.03) | 0.11 (0.01) | 0.062 (0.006) | 0.106 (0.010) | 0.168 (0.018) |
| PF 1 mg | 0.34 (0.01) | 0.11 (0.01) | 0.007 (0.002) | 0.018 (0.004) | 0.020 (0.005) |
| PF 4 mg | 0.32 (0.01) | 0.10 (0.01) | 0.003 (0.001) | 0.011 (0.001) | 0.011 (0.001) |
| PF 20 mg | 0.31 (0.07) | 0.10 (0.01) | 0.005 (0.002) | 0.015 (0.002) | 0.016 (0.003) |
| Occipital cortex | |||||
| Baseline | 0.28 (0.04) | 0.11 (0.01) | 0.061 (0.009) | 0.101 (0.013) | 0.159 (0.021) |
| PF 1 mg | 0.35 (0.04) | 0.12 (0.02) | 0.006 (0.001) | 0.016 (0.003) | 0.016 (0.004) |
| PF 4 mg | 0.31 (0.03) | 0.10 (0.01) | 0.004 (0.001) | 0.011 (0.001) | 0.011 (0.001) |
| PF 20 mg | 0.30 (0.07) | 0.10 (0.01) | 0.006 (0.001) | 0.015 (0.001) | 0.015 (0.001) |
| Parietal cortex | |||||
| Baseline | 0.31 (0.04) | 0.11 (0.01) | 0.063 (0.009) | 0.110 (0.012) | 0.172 (0.019) |
| PF 1 mg | 0.37 (0.01) | 0.12 (0.01) | 0.007 (0.002) | 0.020 (0.003) | 0.021 (0.004) |
| PF 4 mg | 0.33 (0.01) | 0.10 (0.01) | 0.005 (0.001) | 0.014 (0.002) | 0.015 (0.002) |
| PF 20 mg | 0.33 (0.08) | 0.10 (0.01) | 0.005 (0.001) | 0.016 (0.002) | 0.017 (0.002) |
| A. cingulate | |||||
| Baseline | 0.26 (0.02) | 0.11 (0.01) | 0.068 (0.009) | 0.098 (0.007) | 0.159 (0.014) |
| PF 1 mg | 0.31 (0.02) | 0.11 (0.01) | 0.004 (0.001) | 0.010 (0.002) | 0.010 (0.003) |
| PF 4 mg | 0.29 (0.01) | 0.10 (0.01) | 0.004 (0.002) | 0.011 (0.004) | 0.012 (0.004) |
| PF 20 mg | 0.26 (0.07) | 0.09 (0.01) | 0.002 (0.001) | 0.006 (0.003) | 0.006 (0.003) |
| Insular cortex | |||||
| Baseline | 0.27 (0.03) | 0.11 (0.02) | 0.066 (0.009) | 0.106 (0.008) | 0.173 (0.015) |
| PF 1 mg | 0.34 (0.01) | 0.12 (0.01) | 0.007 (0.004) | 0.019 (0.008) | 0.021 (0.009) |
| PF 4 mg | 0.30 (0.01) | 0.09 (0.01) | 0.004 (0.002) | 0.013 (0.006) | 0.013 (0.006) |
| PF 20 mg | 0.30 (0.06) | 0.10 (0.01) | 0.005 (0.001) | 0.015 (0.002) | 0.016 (0.002) |
| Cerebellar cortex | |||||
| Baseline | 0.28 (0.02) | 0.10 (0.01) | 0.057 (0.007) | 0.105 (0.010) | 0.168 (0.017) |
| PF 1 mg | 0.33 (0.01) | 0.10 (0.01) | 0.004 (0.002) | 0.013 (0.003) | 0.013 (0.004) |
| PF 4 mg | 0.28 (0.02) | 0.08 (0.01) | 0.002 (0.001) | 0.008 (0.001) | 0.008 (0.001) |
| PF 20 mg | 0.31 (0.05) | 0.10 (0.01) | 0.005 (0.001) | 0.014 (0.001) | 0.014 (0.001) |
| Hippocampus | |||||
| Baseline | 0.19 (0.03) | 0.09 (0.02) | 0.071 (0.018) | 0.087 (0.009) | 0.160 (0.016) |
| PF 1 mg | 0.23 (0.01) | 0.09 (0.02) | 0.009 (0.005) | 0.019 (0.008) | 0.021 (0.009) |
| PF 4 mg | 0.20 (0.01) | 0.08 (0.01) | 0.006 (0.001) | 0.015 (0.003) | 0.017 (0.004) |
| PF 20 mg | 0.21 (0.04) | 0.08 (0.01) | 0.007 (0.001) | 0.017 (0.003) | 0.018 (0.003) |
| Amygdala | |||||
| Baseline | 0.16 (0.02) | 0.08 (0.05) | 0.069 (0.032) | 0.073 (0.010) | 0.136 (0.020) |
| PF 1 mg | 0.19 (0.01) | 0.08 (0.01) | 0.008 (0.003) | 0.017 (0.006) | 0.019 (0.008) |
| PF 4 mg | 0.17 (0.01) | 0.07 (0.01) | 0.004 (0.002) | 0.010 (0.005) | 0.011 (0.005) |
| PF 20 mg | 0.16 (0.03) | 0.07 (0.01) | 0.007 (0.002) | 0.015 (0.001) | 0.016 (0.002) |
| Caudate | |||||
| Baseline | 0.29 (0.04) | 0.11 (0.03) | 0.057 (0.016) | 0.100 (0.018) | 0.155 (0.030) |
| PF 1 mg | 0.33 (0.03) | 0.10 (0.01) | 0.004 (0.001) | 0.014 (0.003) | 0.014 (0.003) |
| PF 4 mg | 0.31 (0.01) | 0.09 (0.01) | 0.001 (0.001) | 0.005 (0.003) | 0.005 (0.003) |
| PF 20 mg | 0.29 (0.03) | 0.09 (0.01) | 0.003 (0.001) | 0.010 (0.002) | 0.010 (0.002) |
| Putamen | |||||
| Baseline | 0.31 (0.03) | 0.10 (0.01) | 0.056 (0.009) | 0.110 (0.015) | 0.171 (0.028) |
| PF 1 mg | 0.36 (0.01) | 0.10 (0.01) | 0.004 (0.002) | 0.015 (0.007) | 0.015 (0.007) |
| PF 4 mg | 0.34 (0.01) | 0.09 (0.01) | 0.003 (0.001) | 0.010 (0.004) | 0.011 (0.004) |
| PF 20 mg | 0.32 (0.06) | 0.09 (0.01) | 0.003 (0.001) | 0.012 (0.006) | 0.012 (0.007) |
| Thalamus | |||||
| Baseline | 0.31 (0.03) | 0.10 (0.01) | 0.061 (0.009) | 0.117 (0.009) | 0.189 (0.017) |
| PF 1 mg | 0.36 (0.02) | 0.09 (0.01) | 0.005 (0.001) | 0.017 (0.004) | 0.018 (0.005) |
| PF 4 mg | 0.31 (0.02) | 0.07 (0.01) | 0.001 (0.001) | 0.005 (0.003) | 0.005 (0.003) |
| PF 20 mg | 0.33 (0.04) | 0.08 (0.01) | 0.003 (0.001) | 0.011 (0.002) | 0.012 (0.003) |
2-TCMi, irreversible two tissue compartment model; A. cingulate, anterior cingulate cortex; PF, PF-04457845. Data are in mean (s.d.) of n=6 for the baseline and n=2 each after PF-04457845 dosing at 1 mg, 4 mg, and 20 mg, respectively.