Figure 1.

Pharmacokinetic and pharmacodynamic structural models. A. Pharmacokinetic model for doxorubicin (dox) and doxorubicinol (doxo'ol). CL_dox and CL_doxo'ol, elimination clearance of dox and doxo'ol, respectively; fm, fraction metabolized to doxo'ol; Q₂ and Q₃, intercompartmental clearances of doxorubicin; V_C‐dox, V_P2‐dox and V_P3‐dox, the volume of distribution of doxorubicin for central and two peripheral compartments, respectively; V_doxo'ol, the volume of distribution of doxo'ol. B. Pharmacodynamic model of doxorubicin‐induced N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) production. [+ ]: stimulatory effect; dox, doxorubicin; doxo'ol, doxorubicinol; k_in, production rate of the first step in NT‐proBNP synthesis pathway; k_out, degradation rate constant of NT‐proBNP synthesis pathway; k_tr, transit rate constant; NT‐proBNP, NT‐proBNP compartment; Transit 1–5, transit compartment 1–5