Table 1.
Parameter values used for ziprasidone PBPK model
| Parameters | Value | Reference/comments |
|---|---|---|
| MW (g Mol−1) | 412.94 | 31 |
| Log P | 3.60 | 31 |
| Compound type | Monoprotic base | 31 |
| pKa | 6.58 | 31 |
| Absorption | ||
| Model | First‐order | |
| Peff,man (10−4 cm s−1) | 1.66 | Predicted using Papp, Caco‐2 |
| Papp, Caco‐2 (10−6 cm s−1) | 12.30 | 32 |
| fa | 0.90 | 33 |
| k a (h−1) | 0.32 | Adjusted |
| Lag time (h) | 2–3 | 34 |
| fugut | 0.35 | Predicted |
| Qgut (L h−1) | 9.01 | Predicted |
| Distribution | ||
| Model | Full PBPK model | |
| Vss/F (L kg−1) | 1.03 | Predicted using the Rodgers and Rowland method35, 36 |
| fu | 0.01 | 37 |
| B:P | 0.64 | Predicted |
| k p Scalar | 0.63 | Fitted 35, 36 |
| Elimination | ||
| CLiv (L h−1) | 22.80 | 38 |
| % contribution 3A | 33.00 | 39 |
B:P, blood‐to‐plasma partition ratio; CLiv, intravenous clearance; fa, fraction absorbed from dosage form; fu, fraction of drug unbound in plasma; fugut, fraction unbound in the gut; ka, first‐order absorption rate constant; kp, tissue‐plasma partition coefficient; log P, log of the octanol–water partition coefficient for the neutral compound; MW, molecular weight; Papp, Caco‐2, apparent permeability coefficient using CACO‐2 cells; PBPK, physiologically‐based pharmacokinetic; Peff,man, effective permeability in man; pKa, acid dissociation constant; Qgut, gut blood flow; Vss/F, apparent volume of distribution at steady state.