Table 1.
Pharmacokinetic parameters for AZD7325 and GABAA receptor occupancy in four subjects
| Subject | Dose (mg) | C max (nmol/l) | T max (h) | C av,PET (nmol/l) | BPND (baseline) | Occupancy (%) | ||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| OC | CER | PUT | AMG | OC | CER | PUT | AMG | |||||
| 1 | 0.2 | 2.29 | 0.5 | 1.74 | 5.0 | 2.9 | 2.0 | 3.7 | −8 | −5 | 6 | −12 |
| 2 | 0.2 | 4.12 | 0.5 | 2.93 | 5.9 | 3.4 | 2.2 | 4.2 | 0.5 | 3 | −7 | 1 |
| 3 | 1 | 5.19 | 1.8 | 4.97 | 6.0 | 3.0 | 2.5 | 4.5 | 25 | 43 | 35 | 19 |
| 4 | 1 | 12.84 | 1.0 | 10.36 | 5.2 | 2.9 | 2.9 | 4.5 | 11 | 25 | −3 | −14 |
| 3 | 2 | 5.19 | 1.3 | 4.60 | 6.0 | 3.0 | 2.5 | 4.5 | 24 | 45 | 28 | 0.2 |
| 4 | 2 | 21.36 | 1.1 | 15.60 | 5.2 | 2.9 | 2.9 | 4.5 | 42 | 60 | 26 | 17 |
| 1 | 5 | 50.23 | 1.0 | 46.28 | 5.0 | 2.9 | 2.0 | 3.7 | 77 | 85 | 40 | 16 |
| 2 | 5 | 44.02 | 2.2 | 39.22 | 5.9 | 3.4 | 2.2 | 4.2 | 67 | 82 | 37 | 26 |
| 1 | 20 | 213.33 | 3.0 | 57.28 | 5.0 | 2.9 | 2.0 | 3.7 | 75 | 77 | 41 | 9 |
| 2 | 20 | 301.94 | 3.0 | 281.62 | 5.9 | 3.4 | 2.2 | 4.2 | 85 | 95 | 46 | 32 |
| 4 | 30 | 307.58 | 2.2 | 265.25 | 6.0 | 3.0 | 2.3 | 4.5 | 82 | 89 | 52 | 37 |
Receptor occupancy was measured at T max of AZD7325, 1 h after drug administration
C max maximum plasma concentration, T max time for maximum plasma concentration, C av,PET average plasma concentration at time of PET measurement, BP ND binding potential, OC occipital cortex, CER cerebellum, PUT putamen, AMG amygdala