Table 2.
Summary of the median values of pharmacokinetic parameters for risperidone, 9-hydroxyrisperidone and the combination of these two active molecules (as calculated using the “combined” approach) from the Janssen study [18] and the present study of patients administered VAL401
| Parameter | Units | Subjects in the Janssen study [18] | Lung-cancer patients administered VAL401 in the present study (median) | |||||
|---|---|---|---|---|---|---|---|---|
| Young (median) | Elderly (median) | Liver disease (median) | Moderate renal disease (median) | Severe renal disease (median) | All patients (mean + SD) | |||
| Risperidone | ||||||||
| Tmax | h | 1 | 1 | 1 | 1 | 1 | 1 ± 0 | 2 |
| Cmax | ng/ml | 5.33 | 6.37 | 8.16 | 9.6 | 9.65 | 7.8 ± 1.9 | 8* |
| Clast | ng/ml | – | – | – | – | – | – | 1.5* |
| t 1/2 | h | 2.9 | 3.3 | 8.16 | 9.6 | 9.65 | 6.7 ± 3.4 | 3.5 |
| V dss | mL | – | – | – | – | – | – | 113.9 |
| AUC0–∞ | ng·h/mL | 23.5 | 26.2 | 35.9 | 65.8 | 48.6 | 40 ± 17.5 | 58.2* |
| AUC0–last | ng·h/mL | – | – | – | – | – | – | 49.8* |
| AUMC0–∞ | ng·h2/mL | – | – | – | – | – | – | 237.9* |
| Cloral | mL/min | 714 | 642 | 465 | 253 | 343 | 483.4 ± 194.6 | 286.4 |
| MRT | h | – | – | – | – | – | – | 5.1 |
| 9-Hydroxyrisperidone | ||||||||
| Tmax | h | 3 | 2 | 6.5 | 5 | 5 | 4.3 ± 1.8 | 8 |
| Cmax | ng/ml | 4.26 | 5,01 | 2.36 | 5.21 | 5.63 | 4.5 ± 1.3 | 5.8* |
| Clast | ng/ml | – | – | – | – | – | – | 1.8* |
| t1/2 | h | 16.5 | 23.4 | 17.9 | 27.2 | 33.6 | 23.7 ± 7 | 23.4 |
| Vdss | mL | – | – | – | – | – | – | 181 |
| AUC0–∞ | ng·h/mL | 98.7 | 150 | 88.2 | 220 | 257 | 162.8 ± 74.1 | 276.3* |
| AUC0–last | ng·h/mL | – | – | – | – | – | – | 108.1* |
| AUMC0–∞ | ng·h2/mL | – | – | – | – | – | – | 9295.8* |
| Cloral | mL/min | – | – | – | – | – | – | 60.5 |
| MRT | h | – | – | – | – | – | – | 33.8 |
| Total active moiety (risperidone + 9-hydroxyrisperidone) calculated using the “combined” approach | ||||||||
| Tmax | h | 2 | 1.5 | 1 | 1 | 2 | 1.5 ± 0.8 | 3 |
| Cmax | ng/ml | 9.1 | 10.2 | 8.5 | 13 | 13.3 | 13 ± 5.8 | 11.3* |
| Clast | ng/ml | – | – | – | – | – | – | 7.3* |
| t1/2 | h | 17 | 23 | 16 | 25 | 29 | 22 ± 5.5 | 9 |
| Vdss | mL | – | – | – | – | – | – | 73.3 |
| AUC0–∞ | ng·h/mL | 132 | 189 | 145 | 272 | 417 | 231 ± 117.5 | 216.6* |
| AUC0–last | ng·h/mL | – | – | – | – | – | – | 88.3* |
| AUMC0–∞ | ng·h2/mL | – | – | – | – | – | – | 4737.2* |
| Cloral | mL/min | 127 | 89 | 119 | 61 | 40 | 87.2 ± 37.1 | 76.9 |
| MRT | h | – | – | – | – | – | – | 13 |
Subjects in the Janssen study [18] were administered 1 mg risperidone, whereas the patients in the present study were administered 2 mg VAL401. Dose-normalised (to 1 mg of risperidone) VAL401 pharmacokinetic parameter values are reported for Cmax, AUC0–∞, AUC0–last and AUMC0–∞, as indicated by an asterisk
Data on the metabolite (9-hydroxyrisperidone) oral clearance (Cloral) and volume of distribution at steady state (Vdss) were not available for the Janssen study subjects
– Data unavailable