Dear Bob and Simon,
please find below working code I tested it in simulation mode with dummy one line input
id time CObs RATE ProlObs CircObs Aa1 ADDL II
1 0 100 13.88889 4.34 4.94 1000 7 168
it still needs work but it illustrate how e can code transit comparments with a feedback loop.
we can integrate the PK later on currently it has a biomarker linked to the ANC model from a recent publication: http://www.nature.co...psp201362a.html
Samer
test(){
sequence{
BM=BMBASE;
Circ = BASE;
STEM=KE*BASE/KP ;
Transit1=KE*BASE/KP ;
Transit2=KE*BASE/KP;
Transit3=KE*BASE/KP
}
deriv(BM = KIN*(1-EFF) - KOUT*BM )
deriv(Circ = -KE *Circ + KP*Transit3)
deriv(STEM = -KP *STEM + KP*STEM*(1-DRUG)*(BASE/Circ)**0.362)
deriv(Transit1= -KP *Transit1 + KP*STEM )
deriv(Transit2= -KP *Transit2 + KP*Transit1 )
deriv(Transit3= -KP *Transit3 + KP*Transit2 )
error(CEps2 = 0.001)
observe(CircObs = (Circ)+CEps2)
BMCHANGE = ((BM-BMBASE)/BMBASE)
DRUG = 0.520*(-BMCHANGE)/(1.0099+(-BMCHANGE))
EFF = 1*(50/32.819)/(1.0099+(50/32.819))
stparm(KOUT = tvKout )
stparm(KIN = tvKout * BMBASE)
stparm(BMBASE =tvBM0 )
fixef(tvBM0 = c(,42554, ))
fixef(tvKout = c(,0.002719313, ))
FN = (BASE/Circ)**0.362
KP=4/MTT
KE=log(2)/kcirc
stparm(MTT = tvMTT * exp(nMTT))
stparm(kcirc = tvkcirc * exp(nkcirc))
stparm(BASE = tvCirc0* exp(nBASE) )
fixef(tvCirc0 = c(,4.94, ))
fixef(tvMTT = c(, 248, ))
fixef(tvkcirc = c(, 7, ))
ranef(diag( nMTT,nkcirc,nBASE) = c( 1,1,1))
}
