Summary of kinetic parameters for LB and ATV used in PBPK calculation
| Parameter | LB | ATV | Reference/Comment |
|---|---|---|---|
| Molecular weight (g/mol) | 480.5 | 558.6 | DrugBank (http://www.drugbank.ca) |
| Log P | 4.3 | 5.7 | ChemAxon (https://www.chemaxon.com) |
| Compound type | Zwitterions | Monoprotic acid | |
| pKa | |||
| Acid | 7.61 | 4.3 | ChemAxon (https://www.chemaxon.com) |
| Base | 3.96 | ||
| fu,plasma | 0.00267 | 0.0567 | Determineda; Watanabe et al. (2010)b |
| B/P | 0.636 | 1.2 | Determineda; Watanabe et al. (2010)b |
| Distribution | |||
| Kp | 0.0252–2.34 | 0.0270–97.8 | Determined |
| Distribution to liver | |||
| PS (µl/min per 106 cells) | 21.0 ± 6.0 | Determined | |
| Jmax,hepa (pmol/min per 106 cells) | 637 ± 384 | Determined | |
| Km,hepa (µM) | 16.3 ± 10.0 | Determined | |
| Elimination | |||
| Vmax,MIC (pmol/min per mg protein) | 996 | Determined | |
| Km,MIC (µM) | 4.37 | Determined | |
| fu,MIC | 0.479 | 0.557 | Determineda; Watanabe et al. (2010)b |
| CLu,int (ml/min) | 1530 | Calculated using the CL value of ATV from intravenous bolus study with LB coadministration | |
| Inhibition | |||
| Ki,MIC (µM) | 27.0 | Determined | |
| Ki,hepa (µM) | 0.875 ± 0.739 | Determined | |
| Ki,OATP (µM) | 0.296 ± 0.174 | Determined | |
| fu,BSA | 0.111–0.447 | 0.588 | Determined |