system-tumor.txt

# Implementation of the transit model in
#
# Lobo, E.D., Balthasar, J.P. Pharmacodynamic modeling of chemotherapeutic
# effects: Application of a transit compartment model to characterize
# methotrexate effects in vitro. AAPS J 4, 212–222 (2002).
# https://doi.org/10.1208/ps040442
#
#
#
# Initial cell concentrations were taken from the figures 
#  C0 Ehriich ascites: 2.5e3 cells
#  C0 Sarcoma 180:     1.2e3 cells

#
# Sets
#
<SET:TRIN>    K; K1; K2; K3
<SET:TROUT>  K1; K2; K3; K4 

# System parameters
#name     value    lower upper units     edit Grouping 
<P> M      1.0     eps   inf   mcg/ml    yes  System 
<P> kng    0.02    eps   inf   1/hr      yes  System 
<P> tau   34.1     eps   inf   hr        yes  System 
<P> Kmax   0.29    eps   inf   1/hr      yes  System 
<P> EC50   0.1     eps   inf   mcg/ml    yes  System 
<P> C0     2.5e3   eps   inf   mcg/ml    yes  System 
                   
<PSET:default> Ehrlich Ascites Data

<PSET:sarcoma> Sarcoma 180 Data
<PSET:sarcoma:kng>        0.035
<PSET:sarcoma:tau>       30.0
<PSET:sarcoma:Kmax>       0.34
<PSET:sarcoma:EC50>       0.32
<PSET:sarcoma:C0>         1.2e3 

# Here we calculate the kon as a secondary parameter
# for each koff and corresponding KD
<Ad> K = Kmax*M/(EC50 + M)


# Initial number of cells: 
<I> C     = C0

# First we define the transit compartments:
# The following:
SIMINT_SET_ALIGN[TRIN;TROUT][<ODE:{TROUT}> 1.0/tau*({TRIN}-{TROUT})]

# Will expand to:
# <ODE:K1> 1.0/tau*(K-K1)
# <ODE:K2> 1.0/tau*(K1-K2)
# <ODE:K3> 1.0/tau*(K2-K3)
# <ODE:K4> 1.0/tau*(K3-K4)

<ODE:C> kng*C - K4*C

<O> Ncells = C

<TS:hours> 1.0
<TS:days>  1.0/24.0