Exposure-Response Modeling

Modeling dynamic exposure–response relationships 169

uses the same solver and similar model spe cification as in R. For example, to

fit the models:

dR(t)

dt

= E

maxi

/(EC

50

/C(t) + 1) − K

out

R(t)

C(t)

dt

= −θC(t) (6.29)

where E

maxi

|u

i

∼ N(E

max

+ u

i

, σ

e

) is the only ra ndom c oefficient in the

models, the following program, similar to that in Chapter 3, can be used.

bdata=bdata[order(bdata$Subject,bdata$Time),]

gdata=groupedData(conc~Time|Subject,bdata)

OneComp <- list(DiffEq=list(

dy1dt = ~ Emax*y2/(EC50+y2) -kout*y1 , #Absoprtion dynamic

dy2dt = ~ - theta*y2, #Central comp. with elimination rate ke

ObsEq=list(

c1 = ~ y1, #No measure for absorption

c2 = ~ y2, #Observe ...