Table 12.
Typical parameter values, inter-individual and inter-occasion variability, and residual error of the final stepwise model and the single-objective, hybrid genetic algorithm (SOHGA) candidate model with the lowest fitness function value
| Compound | Parameter estimatesa,b,c (relative standard error) | |
|---|---|---|
| Final stepwise model | Best SOHGA candidate model | |
| Citalopram, IV—two compartment | ||
| Clearance (L/h)—TVCL | 7.11 (NA) | 1.22 (5.3 %) |
| Inter-individual variability—ωCL of ηCL | – | – |
| Inter-comp clearance (L/h)—TVQ | 64.4 (NA) | 6.26 (19.0 %) |
| Inter-individual variability—ωQ of ηQ | 48.5 % (NA) | 35.5 % (19.0 %) |
| Central volume (L)—TVV1 | 2.87 (NA) | 82.1 (17.7 %) |
| Inter-individual variability—ωV1 of ηV1 | 12.2 % (NA) | 46.2 % (15.5 %) |
| Peripheral volume (L)—TVV2 | 1,510 (NA) | 205 (12.6 %) |
| Inter-individual variability—ωV2 of ηV2 | 22.6 % (NA) | 25.4 % (12.5 %) |
| Residual variability—σ of ε | σprop = 14.6 % (NA) and | σprop = 10.5 % (28.0 %) |
| σadd = 0.0 μg/L (NA) | – | |
| DMAG—three compartment | ||
| Clearance (L/h)—TVCL | 8.4 (11.2 %) | 9.28 (7.9 %) |
| Inter-patient variability—ωCL of ηCL | 53.8 % (22.9 %) | 22.1 % (29.1 %) |
| Inter-occasion variability—ωCL of ηOCC,CL | – | 8.3 % (38.6 %) |
| First inter-compartment clearance (L/h)—TVQ1 | 85.1 (9.6 %) | 81.0 (8.9 %) |
| Inter-patient variability—ωQ1 of ηQ1 | – | – |
| Inter-occasion variability—ωQ1 of ηOCC,Q1 | 32.6 % (37.2 %) | 14.0 % (32.7 %) |
| Second inter-compartment clearance (L/h)—TVQ2 | 11.6 (13.1 %) | 8.21 (17.4 %) |
| Inter-patient variability—ωQ2 of ηQ2 | 75.8 % (32.0 %) | – |
| First compartment volume (L)—TVV1 | 27.4 (11.7 %) | 28.1 (12.9 %) |
| Inter-patient variability—ωV1 of ηV1 | 33.0 % (111.9 %) | 39.7 % (24.5 %) |
| Inter-occasion variability | 59.7 % (31.2 %) | – |
| Second compartment volume (L)—TVV2 | 66.4 (10.1 %) | 77.9 (11.4 %) |
| Inter-patient variability—ωV2 of ηV2 | 50.7 % (23.7 %) | 42.3 % (24.8 %) |
| Third compartment volume (L)—TVV3 | 142 (13.5 %) | 86.4 (8.5 %) |
| Inter-patient variability—ωV3 of ηV3 | 67.5 % (37.3 %) | – |
| Residual variability—σ of ε | σprop = 16.1 % (2.7 %) | σprop = 2.1 % (13.2 %) and |
| – | σadd = 24.7 μg/L (69.6 %) | |
| Escitalopram, oral—one compartment with absorption | ||
| Clearance (L/h)—TVCL | – | 25.5 (5.3 %) |
| Extensive metabolizer | 26 (7.20 %) | – |
| Poor metabolizer | 19.8 (8.50 %) | – |
| Missing metabolizer information | 21.5 (7.80 %) | – |
| Inter-individual variability—ωCL of ηCL | 48.5 % (15.1 %) | 48.8 % (12.3 %) |
| Volume of distribution (L)—TVV | 947 (10.2 %) | 874 (11.8 %) |
| Inter-individual variability—ωV of ηV | 62.0 % (40.3 %) | 59.4 % (32.6 %) |
| Absorption (1/h)—TVKA | 0.8 (NA) | 0.594 (23.1 %) |
| Inter-individual variability—ωKA of ηKA | 78.9 % (87.0 %) | – |
| Residual variability—σ of ε | σprop = 28.9 % (8.8 %) | σprop = 28.8 % (11.1 %) and |
| – | σadd = 70.4 μg/L (131 %) | |
| Olanzapine, oral—one compartment with absorption | ||
| Clearance (L/h)—TVCL | 16.1 (7.3 %) | 21.1 (15.5 %) |
| Inter-individual variability—ω CL of η CL | 68 % | 64.7 % (17.2 %) |
| Volume of distribution (L)—TVV | 2,150 (26.0 %) | 4,130 (48.9 %) |
| Inter-individual variability—ωV of ηV | 86 % | – |
| Absorption rate constant (1/h)—TVKA | Fixed at 0.5 | 0.773 (70.4 %) |
| Inter-individual variability—ωKA of ηKA | – | – |
| Residual variability—σ of ε | – | σprop = 37.7 % (14.5 %) and σadd = 275 μg/L (50.9 %) |
| σadd = 212 μg/L (1.7 %) | ||
| Perphenazine, oral—one compartment with absorption | (95 % CI from bootstrapping) | |
| Clearance (L/h)—TVCL | 483 | 354 (12.3 %) |
| Inter-individual variability—ωCL of ηCL | 79.3 % (68.1 - 87.4 %) | 78.8 % (11.4 %) |
| Volume of distribution (L)—TVV | 18,200 (13,865 - 65,795) | 1.10x107 (172 %) |
| Inter-individual variability—ωV of ηV | 78.5 % (20 - 120 %) | – |
| Absorption rate constant (1/h)—TVKA | Fixed at 1.6 | 0.859 (80.7 %) |
| Inter-individual variability—ωKA of ηKA | 336.1 % (0.35 - 518 %) | – |
| Residual variability—σ of ε | σprop = 37.4 % (33.3 - 41.0 %) | σprop = 37.1 % (10.5 %) |
| Risperidone, oral—one compartment with absorption | 3 component mixture for clearance | 3 component mixture for clearance |
| Percent of subjects who were poor metabolizers | 41.2 % (8.1 %) | 22.4 % (4.4 %) |
| Percent of subjects who were extensive metabolizers | 52.4 % (6.2 %) | 41.4 % (8.6 %) |
| Clearance (L/h)—TVCL | – | – |
| Poor metabolizer | 12.9 (6.5 %) | 12.4 (8.5 %) |
| Intermediate metabolizer | Fixed at 36 | 34.9 (8.9 %) |
| Extensive metabolizer | 65.4 (9.9 %) | 122 (11.5 %) |
| Inter-individual variability—ωCL of ηCL | – | 7.3 % (32.2 %) |
| Poor metabolizer | 95.9 % (39.5 %) | – |
| Intermediate metabolizer | NA (NA) | – |
| Extensive metabolizer | 56.6 % (16.8 %) | – |
| Volume of distribution (L)—TVV | 444 (17.8 %) | – |
| Inter-individual variability—ωV of ηV | 36.1 % (24.4 %) | – |
| Central volume—TVV1 | – | 96.6 (31.2 %) |
| Inter-individual variability—η(V1) | – | 478 % (46.4 %) |
| Inter-comp clearance—TVQ | – | 27.1 (29.9 %) |
| Inter-individual variability—η(Q) | – | – |
| Peripheral volume—TVV2 | – | 1.31x1010 (1,000 %) |
| Inter-individual variability—η(V2) | – | – |
| Absorption rate constant (1/h)—TVKA | Fixed at 1.7 | 0.184.(21.1 %) |
| Inter-individual variability—ωKA of ηKA | 53.7 % (89.3 %) | – |
| Residual variability—σ of ε | σprop = 63.9 % (12.5 %) and | σprop = .39.8 % (9.3 %) |
| σadd = 4.29 μg/L (104.9 μg/L) | – | |
| Ziprasidone, oral—one compartment with absorption | ||
| Clearance (L/h)—TVCL | 122 (9 %) | 126 (9.0 %) |
| Inter-individual variability—ωCL of ηCL | 64.8 % (25 %) | 69.0 % (21.4 %) |
| Volume of distribution (L)—TVV | 1,060 (19 %) | 1,030 (12.4 %) |
| Inter-individual variability—ωV of ηV | 104.4 % (27 %) | 114 % (16.0 %) |
| Absorption rate constant (1/h)—TVKA | Fixed at 0.5 | 0.424 (5.8 %) |
| Inter-individual variability—ωKA of ηKA | – | – |
| Residual variability—σ of ε | σprop = 65.5 % (8 %) | σprop = 65.1 % (8.3 %) |
aParameter estimates denoted by “–” were not calculated and standard errors denoted by “NA” are not available because the covariance matrix did not converge
bThe reported inter-individual variability value is the standard deviation (ω) of the random inter-individual variability variable (η), which is a normal distribution with near zero mean
cThe reported residual variability value is the standard deviation (σ) of the residual variability variable (ε), which is a normal distribution with near zero mean