Pharmacokinetic parameters following intramuscular injection of CNO-DMSO or CNO-HCl
Data are presented as mean ± S.D.
| Drug/Dose | Cmaxa | Tmaxa | AUC60–240a | Half-Lifeb | Vd (Observed)c | CL (Observed)c |
|---|---|---|---|---|---|---|
| mg/kg | ng/ml | min | μg/ml⋅min | min | l | l/min |
| Plasma CNO | ||||||
| CNO-DMSO | ||||||
| 3.0 | 226 ± 20 | 75 ± 21 | 25 ± 2 | 82 ± 5 | 75 ± 29 | 0.6 ± 0.2 |
| 5.0 | 415 ± 197 | 75 ± 21 | 50 ± 22 | 1391 ± 1817 | 98 ± 37 | 0.4 ± 0.6 |
| 7.0 | 595 ± 308 | 75 ± 21 | 65 ± 32 | 137 ± 99 | 103 ± 92 | 0.5 ± 0.1 |
| CNO-HCl | ||||||
| 3.0 | 1399 ± 754 | 65 ± 12 | 110 ± 53 | 69 ± 11 | 18 ± 12 | 0.2 ± 0.1 |
| 5.6 | 1932 ± 704 | 85 ± 12 | 207 ± 84 | 106 ± 55 | 25 ± 20 | 0.2 ± 0.0 |
| 10 | 3191 ± 1558 | 75 ± 16 | 300 ± 200 | 72 ± 24 | 20 ± 7 | 0.2 ± 0.1 |
| Plasma clozapine | ||||||
| CNO-DMSO | ||||||
| 3.0 | 8.7 ± 0.4 | 90 ± 0 | 1.5 ± 0.007 | — | — | — |
| 5.0 | 16.4 ± 2.1 | 165 ± 106 | 2.4 ± 0.014 | — | — | — |
| 7.0 | 22.6 ± 1.2 | 90 ± 0 | 3.7 ± 0.2 | — | — | — |
| CNO-HCl | ||||||
| 3.0 | 15 ± 2.9 | 160 ± 88 | 2.5 ± 0.5 | — | — | — |
| 5.6 | 27.9 ± 5.7 | 140 ± 77 | 4.3 ± 0.8 | — | — | — |
| 10 | 39.0 ± 4.4 | 190 ± 77 | 6.1 ± 0.7 | — | — | — |
| Clozapine:CNO (%) | ||||||
| CNO-DMSO | ||||||
| 3.0 | 16.2 ± 3.9 | 240 ± 0 | 1.6 ± 0.3 | — | — | — |
| 5.0 | 9.4 ± 7.2 | 240 ± 0 | 1.2 ± 0.7 | — | — | — |
| 7.0 | 14.7 ± 4.5 | 240 ± 0 | 1.7 ± 0.06 | — | — | — |
| CNO-HCl | ||||||
| 3.0 | 8.4 ± 2.3 | 240 ± 0 | 0.8 ± 0.3 | — | — | — |
| 5.6 | 7.4 ± 2.2 | 165 ± 106 | 0.8 ± 0.2 | — | — | — |
| 10 | 9.9 ± 5.8 | 240 ± 0 | 0.9 ± 0.5 | — | — | — |
CL, clearance; Cmax, peak plasma concentration; Tmax, time of peak plasma concentration; Vd, volume of distribution; —, V, CL, and half life were only calculated for the administered drug, CNO.
↵a Only data from sampling time points that were common to both forms of the drug were included in these calculations (60, 90, and 240 min postdrug administration).
↵b Terminal half-life was calculated using all three samples: 60, 90, and 240 min post-injection.
↵c The V and CL values were estimated from intramuscular injections based on the observed fraction of drug absorbed.