Table 11.
Model structures and covariates of the final stepwise model and the single-objective, hybrid genetic algorithm (SOHGA) candidate model with the lowest fitness function value
| Compounds | Covariates in stepwise model (abbreviation of function forma) | Covariates in the best SOHGA candidate model (abbreviation of function forma) |
|---|---|---|
| Citalopram, IV | ADVAN3, TRANS4 (2 compartments) | ADVAN3, TRANS4 (2 compartments) |
| Clearance—TVCL | Weight (pow) | – |
| Inter-individual variability—η(CL) | – | – |
| Central volume—TVV1 | Sex (add) | Sex (exp), body-mass index (exp) |
| Inter-individual variability—η(V1) | Exponential | Exponential |
| Inter-comp clearance—TVQ | Fat mass (exp) | Fat mass (prop), fat-free mass (exp) |
| Inter-individual variability—η(Q) | Exponential | Exponential |
| Peripheral volume—TVV2 | Weight (pow) | Fat (exp), fat-free mass (exp) |
| Inter-individual variability—η(V2) | Exponential | Exponential |
| Residual variability—ε(1) and ε(2) | Combined | Proportional |
| DMAG, IV | ADVAN11, TRANS4 (3 compartments) | ADVAN11, TRANS4 (three compartments) |
| Clearance—TVCL | – | Sex (exp) |
| Inter-individual variability—η(CL) | Exponential | Exponential |
| Inter-occasion variability—η(OCC,CL) | – | Exponential |
| First comp clearance—TVQ1 | – | – |
| Inter-individual variability—η(Q1) | – | – |
| Inter-occasion variability—η(OCC,Q1) | Exponential | Exponential |
| Second comp clearance—TVQ2 | – | – |
| Inter-patient variability—η(Q2) | Exponential | – |
| Central volume—TVV1 | – | – |
| Inter-individual variability—η(V1) | Exponential | Exponential |
| Inter-occasion variability—η(OCC,V1) | Exponential | – |
| Peripheral volume—TVV2 | – | – |
| Inter-individual variability—η(V2) | Exponential | Exponential |
| Third volume—TVV3 | – | – |
| Inter-patient variability—η(V3) | Exponential | – |
| Residual variability—ε(1) and ε(2) | Proportional | Combined |
| Escitalopram, oral | ADVAN2, TRANS2 [17] (one compartment with absorption) | ADVAN2, TRANS2 (one compartment with absorption) |
| Clearance—TVCL | Age (pow), genotype (add), weight (pow) | Age (pow), site (add) |
| Inter-individual variability—η(CL) | Exponential | Exponential |
| Volume of distribution—TVV | Body mass index (pow) | Body mass index (pow) |
| Inter-individual variability—η(V) | Exponential | Exponential |
| Absorption rate constant—TVKA | – | – |
| Inter-individual variability—η(KA) | Exponential | – |
| Residual variability—ε(1) and ε(2) | Proportional | Combined |
| Olanzapine, oral | ADVAN2, TRANS2 [10] (one compartment with absorption) | ADVAN2, TRANS2 (one compartment with absorption) |
| Clearance—TVCL | Race (add), sex (add), smoking status (add) | Age (add), sex (add) |
| Inter-individual variability—η(CL) | Exponential | Exponential |
| Volume of distribution—TVV | – | – |
| Inter-individual variability—η(V) | Exponential | – |
| Absorption rate constant—TVKA | Unstable: fixed based on literature | – |
| Inter-individual variability—η(KA) | – | – |
| Residual variability—ε(1) and ε(2) | Additive | Combined |
| Perphenazine, oral | ADVAN2, TRANS2 [11] (one compartment with absorption) | ADVAN2, TRANS2 (one compartment with absorption) |
| Clearance—TVCL | Race (add), smoking status (add) | Fluoxetine use (exp), number of cigarettes per day (exp), race (exp), smoking status (prop) |
| Inter-individual variability—η(CL) | Exponential | Exponential |
| Volume of distribution—TVV | – | Age (exp), sex(exp), and smoking status (prop) |
| Inter-individual variability—η(V) | Exponential | – |
| Absorption rate—TVKA | Unstable: fixed based on literature | – |
| Inter-individual variability—η(KA) | Exponential | – |
| Residual variability—ε(1) and ε(2) | Proportional | Proportional |
| Risperidone, oral | ADVAN2, TRANS2 with three component clearance mixture [12] (one compartment with absorption) | ADVAN4, TRANS4 with three component mixture on clearance (two compartment with absorption) |
| Clearance—TVCL | – | Age (exp), fluoxetine use (exp), paroxetine use (exp), race (exp) |
| Inter-individual variability—η(CL) | Exponential | Exponential |
| Volume of distribution—TVV | – | – |
| Inter-individual variability—η(V) | Exponential | – |
| Central volume—TVV1 | – | – |
| Inter-individual variability—η(V1) | – | Exponential |
| Inter-comp clearance—TVQ | – | – |
| Inter-individual variability—η(Q) | – | – |
| Peripheral volume—TVV2 | – | – |
| Inter-individual variability—η(V2) | – | – |
| Absorption rate constant—TVKA | Fixed based on literature | – |
| Inter-individual variability—η(KA) | Exponential | – |
| Residual variability—ε(1) and ε(2) | Combined | Proportional |
| Ziprasidone, oral | ADVAN2, TRANS2 [13] (one compartment with absorption) | ADVAN2, TRANS2 (one compartment with absorption) |
| Clearance—TVCL | – | – |
| Inter-individual variability—η(CL) | Exponential | Exponential |
| Volume of distribution—TVV | – | – |
| Inter-individual variability—η(V) | Exponential | Exponential |
| Absorption rate constant—TVKA | Unstable: fixed based on literature | – |
| Inter-individual variability—η(KA) | – | – |
| Residual variability—ε(1) and ε(2) | Proportional | Proportional |
aAbbreviations for functional forms include: add additive, prop proportional, exp exponential, pow power-law