Table 2.

Structural models considered for fluconazole pharmacokinetics

Model	Description	Exposure	Models	Parameter values
M1	One-compartment model with linear input and disposition, high CL	Low (AUC 40%↓)		CL = 1.32 l h−1F = 0.8 BSVF = 32%
M2	One-compartment model with linear input and disposition, low CL	High (AUC 40%↑)		CL = 0.67 l h−1F = 0.8 BSVF = 32%
M3	One-compartment model with nonlinear input and linear disposition, high Fmin	Low (AUC 40%↓) Dose = 400 mg		CL = 0.94 l h−1Fmin = 0.8 × FabsKmn = 470 BSVF = 32%
M4	One-compartment model with nonlinear input and linear disposition, low Fmin	Low (AUC 30%↓) Dose = 400 mg		CL = 0.94 l h−1Fmin = 0.6 × FabsKmn = 470 BSVF = 32%
M5	One-compartment model with linear input and nonlinear disposition	Low (AUC 40%↓)		Fmaxreabs = 0.8 Kml = 0.8 CL_int = 7.2 F = 0.8 BSVFmaxreabs = 22% BSVF = 32% BSVCL_int = 32%

↓, reduced; ↑, increased; AUC, area under the curve; F_min, the minimum reabsorbed fraction; F_abs, fraction absorbed; Km_n, the dose at half F_min in the nonlinear input and linear disposition models (M3, M4); Km₁, drug concentration in central compartment at half CL_rmax in the linear input and nonlinear disposition model (M5); CL_reabs, reabsorbed clearance; CL_rmax, the maximum reabsorbed clearance; [central cpt], the drug concentration in the central compartment. The column ‘Parameter values’ shows the values of the parameters that were perturbed from the values given in Table 1.