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. 2014 Jun 25;3(6):e120. doi: 10.1038/psp.2014.18

Figure 1.

Figure 1

Diagram of CYP3A4 semi-mechanistic PK/PD model for CYP3A4 interactions. 4αHC, 4α-hydroxycholesterol; 4βHC, 4β-hydroxycholesterol; CKeto, concentration of ketoconazole; CL, clearance from central compartment; CLINT, intrinsic clearance; CMDZ, concentration of MDZ; CYP, fold induction in CYP3A4; FPE, first-pass effect for MDZ; Fu, fraction unbound for MDZ; Fuk, fraction unbound for ketoconazole; INH4βHC, inhibition function for effect of ketoconazole on formation of 4β-hydroxycholesterol; INHMDZ, inhibition function for effect of ketoconazole on midazolam's intrinsic clearance; Kc, central compartment for ketoconazole; Kdeg,4αHC, elimination rate for 4α-hydroxycholesterol; Kdeg,4βHC, elimination rate for 4β-hydroxycholesterol; Ki, inhibition constant for ketoconazole; Km, concentration for half maximal metabolic clearance rate; Kp, peripheral compartment for ketoconazole; Ksyn, synthesis rate for 4β-hydroxycholesterol in the absence of induction or inhibition; Ksyn,4αHC, synthesis rate for 4α-hydroxycholesterol; Ksyn,4βHC, synthesis rate for 4β-hydroxycholesterol; Ksyn,TC, synthesis rate for total cholesterol; KTR, gut transit rate constant; Mc, central compartment for MDZ; Mp, peripheral compartment for MDZ; MTT, mean transit time in gut; N, number of compartments; QH, hepatic blood flow; Rif, rifampin; Vc, volume of central compartment; Vmax, maximum rate of metabolic clearance.