; =============================================
DESCRIPTION: Neutropenia
  Example neutropenia model
  Dose unit: mg
  Output unit: 10^9 cells/L
  Time unit: hours
; =============================================

  [LONGITUDINAL]

  input = {CIRC0,MTT,SLOPU,GAM,Vp,Vc,CL,Q}
  Vp = {use=regressor}
  Vc = {use=regressor}
  CL = {use=regressor}
  Q = {use=regressor}

; =============================================
PK:
; =============================================

  ; Model parameters
  ; ----------------
  Tlag1 = 0

  ; Model compartments
  ; ------------------
  compartment(cmt=1, amount=A_centr)
  compartment(cmt=2, amount=A_periph)
  compartment(cmt=3, amount=A_prol)
  compartment(cmt=4, amount=A_tr1)
  compartment(cmt=5, amount=A_tr2)
  compartment(cmt=6, amount=A_tr3)
  compartment(cmt=7, amount=A_circ)

  ; Model dosing
  ; ------------
  iv(cmt=1, type=1, p=1, Tlag=Tlag1)

; =============================================
EQUATION:
; =============================================

  ; Start time of integration
  ; -------------------------
  ; Integration starts with first event in subject

  ; Define type of solver
  ; ---------------------
  odeType = stiff

  ; Model variables
  ; ---------------
  CONC = A_centr/Vc
  KTR = 4/MTT

  ; Initial conditions
  ;------------------
  A_centr_0 = 0
  A_periph_0 = 0
  A_prol_0 = CIRC0
  A_tr1_0 = CIRC0
  A_tr2_0 = CIRC0
  A_tr3_0 = CIRC0
  A_circ_0 = CIRC0
  
  ; Differential equations
  ; ----------------------
  ddt_A_centr = -CL/Vc*A_centr-Q/Vc*A_centr+A_periph*Q/Vp
  ddt_A_periph = Q/Vc*A_centr-A_periph*Q/Vp
  ddt_A_prol = KTR*A_prol*(1-SLOPU*CONC)*(CIRC0/A_circ)^GAM-KTR*A_prol
  ddt_A_tr1 = KTR*A_prol-KTR*A_tr1
  ddt_A_tr2 = KTR*A_tr1-KTR*A_tr2
  ddt_A_tr3 = KTR*A_tr2-KTR*A_tr3
  ddt_A_circ = KTR*A_tr3-KTR*A_circ

; =============================================
OUTPUT:
; =============================================

  output = {A_circ}