********** MODEL NAME model_1cpt_abs1_enzyme_autoinduction ********** MODEL NOTES PK model for simulation of drug concentration in central compartment with following characteristics: Compartments: 1 Elimination : Enzyme utoinduction Absorption : first order (with lag time) Unit convention Dose: mg Concentration: ug/mL Time: hours The annotation of the parameter units is consistent with the given unit convention. Units of the inputs (dose) and outputs (concentration) in the dataset for parameter estimation need to match the unit convention. ********** MODEL STATES d/dt(Ad) = -kabs*Ad + Fabs1*INPUT1 d/dt(Ac) = kabs*Ad - CL/Vc*Ac d/dt(Enz) = Kenz*INH-Kenz*Enz Ad(0) = 0 Ac(0) = 0 Enz(0) = 1 ********** MODEL PARAMETERS Fabs1 = 1 # Relative bioavailability (-) kabs = 0.35 # Absorption rate parameter (1/hour) CL2 = 0.103 # Apparent clearance (L/hour) CLINT = 1.23 # Clearance inducted (L/hour) Vc = 32 # Apparent central volume (L) Tlag1 = 0 # Absorption lag time (hours) Kenz = 0.081 # Enzyme rate constant (1/hours) KM = 0.56 # KM (mg/L) IMAX = 1 # Maximum inhibition clearance ********** MODEL VARIABLES % Calculation of concentration in central compartment Cc = Ac/Vc INH = 1-(IMAX*Cc/(KM+Cc)) CL1 = CLINT*Enz CL = CL1+CL2 % Defining an output (only needed when interfacing with NLME % parameter estimation tools such as NONMEM and MONOLIX) OUTPUT1 = Cc # Compound concentration (ug/mL) ********** MODEL REACTIONS ********** MODEL FUNCTIONS ********** MODEL EVENTS