Figure 1.

A diagrammatic representation of the final semiphysiologically based pharmacokinetic model that includes S‐ketamine model, norketamine model, ticlopidine model, and a dynamic drug‐drug interaction model. A _H, reversible component of CYP2B6 inhibition; B _H, the non‐reversible component of CYP2B6 inhibition; C, central compartment; CL_INT, intrinsic clearance; CYP, cytochrome P450; D, amount of inhibitor (ticlopidine) administered; F, bioavailability of ticlopidine into the first depot compartment; $f_{{{\mathrm{CL}}^{\prime }}_{\mathrm{INT},\mathrm{H}}}$, inhibition parameter signifying hepatic CYP2B6 degradation; f _m,CYP2B6, fraction of S‐ketamine metabolized by CYP2B6; f _u, fraction unbound of ticlopidine in the blood; GW, gut wall; H, hepatic; [I], ticlopidine concentration at the enzyme site; [I]_PV, ticlopidine concentration at the portal vein; k _a, absorption rate constant; k _deg, the physiological degradation rate of CYP2B6 at inhibitor concentration of [I] = 0; K _I, degradation rate of CYP2B6 at inhibitor concentration of [I]; k _i, the dissociation constant of ticlopidine for CYP2B6; k _inact, the maximal inhibition rate achieved at inhibitor concentration [I] = ∞; NK, norketamine; PER1, first peripheral compartment; PER2, second peripheral compartment; PV, portal vein; Q, blood flow; SK, S‐ketamine; TIC, ticlopidine; V, volume; VI, gut wall villous mucosa.