Figure 1.

Simulated propafenone metabolism under in vitro (CYP2D6 = 0.0017 µM) and in vivo (CYP2D6 = 0.95 µM) conditions. (a) The canonical model (Eq. 4) accurately simulates propafenone metabolism under the in vitro condition, but not the in vivo condition (inset). Here, $S_{\mathrm{T}}$ represents the initial drug concentration. For the simulations, $V_{max}=4.83$ pmol∙min⁻¹∙pmol⁻¹ CYP and $K_{\mathrm{M}}=0.12\mu M$ are used based on the experimental measurement (Table 1 and S1 ). $E_{\mathrm{T}}=0.0017\mu M$ ²² and $E_{\mathrm{T}}=0.95\mu M$ are used for in vitro and in vivo simulations, respectively (Table 1 ). $k_{\mathrm{f}}=100\mu M/min$ and $k_{\mathrm{b}}=7.17$ min⁻¹ are used for the full model (Eq. 8 in Supplementary Note ) simulation so that $K_{\mathrm{M}}=0.12\mu M$ . $S(0)=0.01$ µM, $C(0)=0$ and $P(0)=0$ . (b) The new model (Eq. 6) accurately simulates the drug metabolism under both in vitro and in vivo conditions (inset). K _M, Michaelis‐Menten constant; V _max, maximal rate of metabolism.