Table 3.
Predicted and observed pharmacokinetic parameters of ziprasidone in different populations and doses. Results expressed as mean predicted (pred) and observed (obs) parameters
| Population | Study reference | Dose | AUC (ng ml −1 h −1 ) a | C max (ng ml −1 ) | t max (h) | |
|---|---|---|---|---|---|---|
| Healthy adult volunteers | 31 | 20 mg, i.v. single dose | Observed | 817.68 | 297.05 | 0.93 |
| Predicted | 891.99 | 415.33 | 1.00 | |||
| Pred/obs ratio | 1.09 | 1.40 | 1.08 | |||
| Single i.v. dose MFE | 1.09 | 1.40 | 1.08 | |||
| 38 | 20 mg, oral single dose | Observed | 514.00 | 64.00 | 8.20 | |
| Predicted | 349.74 | 43.21 | 5.74 | |||
| Pred/obs ratio | 0.68 | 0.68 | 0.70 | |||
| 43 | 5 mg, oral single dose | Observed | 86.70 | 12.20 | 5.00 | |
| Predicted | 88.85 | 11.03 | 3.73 | |||
| Pred/obs ratio | 1.02 | 0.90 | 0.75 | |||
| 20 mg, oral single dose | Observed | 226.30 | 26.60 | 4.80 | ||
| Predicted | 347.36 | 43.10 | 3.73 | |||
| Pred/obs ratio | 1.53 | 1.62 | 0.78 | |||
| 20 mg, oral single dose | Observed | 376.70 | 60.00 | 3.80 | ||
| Predicted | 359.42 | 44.58 | 3.75 | |||
| Pred/obs ratio | 0.95 | 0.74 | 0.99 | |||
| 20 mg, oral single dose | Observed | 308.40 | 34.30 | 4.00 | ||
| Predicted | 349.44 | 43.31 | 3.71 | |||
| Pred/obs ratio | 1.13 | 1.26 | 0.93 | |||
| 44 | 20 mg, oral single dose | Observed | 467.00 | 50.00 | 5.60 | |
| Predicted | 358.89 | 44.70 | 3.76 | |||
| Pred/obs ratio | 0.77 | 0.89 | 0.67 | |||
| 40 mg, oral single dose | Observed | 902.00 | 87.00 | 6.40 | ||
| Predicted | 710.82 | 88.09 | 4.76 | |||
| Pred/obs ratio | 0.79 | 1.01 | 0.74 | |||
| 80 mg, oral single dose | Observed | 1911.00 | 165.00 | 6.60 | ||
| Predicted | 1421.64 | 176.18 | 4.76 | |||
| Pred/obs ratio | 0.74 | 1.07 | 0.72 | |||
| 37 | 20 mg, single dose oral | Observed | 344.00 | 56.00 | 4.00 | |
| Predicted | 271.15 | 42.61 | 3.58 | |||
| Pred/obs ratio | 0.79 | 0.76 | 0.90 | |||
| Single oral dose MFE | 0.94 | 0.99 | 0.80 | |||
| 43 | 5 mg, b.i.d. | Observed | 109.80 | 14.80 | 5.20 | |
| Predicted | 88.88 | 12.95 | 3.53 | |||
| Pred/obs ratio | 0.81 | 0.88 | 0.68 | |||
| 20 mg, b.i.d. | Observed | 259.20 | 44.60 | 3.80 | ||
| Predicted | 347.58 | 50.66 | 3.53 | |||
| Pred/obs ratio | 1.34 | 1.14 | 0.93 | |||
| 40 mg, b.i.d. | Observed | 658.00 | 118.60 | 3.70 | ||
| Predicted | 719.34 | 104.65 | 3.55 | |||
| Pred/obs ratio | 1.09 | 0.88 | 0.96 | |||
| 60 mg, b.i.d. | Observed | 1027.90 | 139.40 | 4.70 | ||
| Predicted | 1048.85 | 152.93 | 3.51 | |||
| Pred/obs ratio | 1.02 | 1.10 | 0.75 | |||
| 44 | 40 mg, b.i.d. | Observed | 940.00 | 163.00 | 3.40 | |
| Predicted | 672.76 | 99.44 | 3.29 | |||
| Pred/obs ratio | 0.72 | 0.61 | 0.97 | |||
| 37 | 20 mg, b.i.d. | Observed | 465.00 | 69.00 | 4.00 | |
| Predicted | 344.65 | 50.49 | 3.38 | |||
| Pred/obs ratio | 0.74 | 0.73 | 0.85 | |||
| Oral dose b.i.d. (SS) MFE | 0.95 | 0.89 | 0.85 | |||
| Paediatric | 45 | 5 mg, oral single dose | Observed | 247.00 | 36.00 | 5.00 |
| Predicted | 259.59 | 37.90 | 3.39 | |||
| Pred/obs ratio | 1.05 | 1.05 | 0.68 | |||
| 10 mg, oral single dose | Observed | 338.00 | 45.00 | 5.10 | ||
| Predicted | 366.10 | 50.15 | 3.57 | |||
| Pred/obs ratio | 1.08 | 1.11 | 0.70 | |||
| 20 mg, oral single dose | Observed | 457.00 | 51.00 | 5.50 | ||
| Predicted | 581.07 | 73.84 | 3.72 | |||
| Pred/obs ratio | 1.27 | 1.44 | 0.67 | |||
| Single oral dose MFE—paediatric | 1.11 | 1.17 | 0.69 | |||
| Geriatric | 37 | 20 mg, oral single dose | Observed | 382.00 | 60.00 | 5.00 |
| Predicted | 269.46 | 42.54 | 3.50 | |||
| Pred/obs ratio | 0.71 | 0.71 | 0.70 | |||
| Single oral dose MFE—geriatric | 0.71 | 0.71 | 0.70 | |||
| 20 mg, b.i.d. | Observed | 560.00 | 85.00 | 4.00 | ||
| Predicted | 354.20 | 51.52 | 3.30 | |||
| Pred/obs ratio | 0.63 | 0.61 | 0.83 | |||
| Oral dose b.i.d. (SS) MFE—geriatric | 0.63 | 0.61 | 0.83 | |||
AUC, area under the plasma concentration–time curve; b.i.d., twice daily; C max, maximum concentration; i.v., intravenous; MFE, mean fold error; SS, steady‐state; t max, time to maximum concentration.
a
0–∞ for single dose studies and 0–12 h for multiples dose twice‐daily studies.
Note: Virtual trials were conducted in 100 (10 × 10) subjects randomly selected by simulator the proportion of female and age were fitted to match the observed data.