********** MODEL NAME Neutropenia ********** MODEL NOTES Example neutropenia model Dose unit: mg Output unit: 10^9 cells/L Time unit: hours ********** MODEL STATES # Differential equations PK model d/dt(A_centr) = - CL/Vc*A_centr - Q/Vc*A_centr + A_periph*Q/Vp + INPUT1 d/dt(A_periph) = Q/Vc*A_centr - A_periph*Q/Vp # Differential equations Friberg model d/dt(A_prol) = KTR*A_prol*(1-SLOPU*CONC)*(CIRC0/A_circ)^GAMMA - KTR*A_prol d/dt(A_tr1) = KTR*A_prol - KTR*A_tr1 d/dt(A_tr2) = KTR*A_tr1 - KTR*A_tr2 d/dt(A_tr3) = KTR*A_tr2 - KTR*A_tr3 d/dt(A_circ) = KTR*A_tr3 - KTR*A_circ # Initial conditions A_prol(0) = CIRC0 A_tr1(0) = CIRC0 A_tr2(0) = CIRC0 A_tr3(0) = CIRC0 A_circ(0) = CIRC0 ********** MODEL PARAMETERS # Define parameters CIRC0 = 7.21 # Baseline circulating neutrophils (10^9 cells/L) MTT = 124 # Mean transit time (hours) SLOPU = 28.9 # Slope of drug effect (mL/ug) GAMMA = 0.239 # Exponent (.) # Define regression parameters Vp = 1 # Peripheral volume (L) Vc = 1 # Central volume (L) CL = 1 # Clearance (L/hour) Q = 1 # Intercompartmental clearance (L/hour) ********** MODEL VARIABLES # Calculate central concentration CONC = A_centr/Vc # PD parameters KTR = 4/MTT # Output for fitting OUTPUT1 = A_circ # (10^9 cells/L) Circulating neutrophils ********** MODEL REACTIONS ********** MODEL FUNCTIONS ********** MODEL EVENTS