Table 2 Physicochemical, physiological, and pharmacokinetic input parameters used for the development of the PBPK model of clozapine.
Parameter | Value | Source |
|---|---|---|
Log P | 3.500 | Lee et al.4 |
pKa | 7.500 | Lee et al.4 |
Molecular weight (MW) (g/mol) | 326.823 | ADMET predictor™ |
Aqueous solubility (S) (mg/mL) | 0.186 | Tassaneeyakul et al.59 |
Dosage form | TD: Reservoir Patch | Adjusted |
Dosing region | Arm | Adjusted |
Application surface area (cm2) | 9 | Adjusted |
Jejunal effective permeability (Peff) (cm/s × 10–4) | 6.862 | Lee et al.4 |
Unbound percent in human plasma (% Fup) | 3% | Lee et al.4 |
Human blood to plasma concentration ratio (Rbp) | 0.845 | Lee et al.4 |
Stratum corneum diffusivity (cm2/s) | 1.294 E-11 | TCAT® model |
Epidermis diffusivity (cm2/s) | 3.92E-07 | TCAT® model |
Dermis diffusivity (cm2/s) | 2.14E-04 | Calculated |
t1/2 (h) | 5.035 | PKPlus™ |
K12 | 0.063 | PKPlus™ |
K21 | 0.0057 | PKPlus™ |
Clearance (CL) (L/h) | 31.750 | DrugBank60 |
