[R] Changing state in ODE

[Paul Hutson]

I am trying to fit data from human and animal pharmacokinetic studies in 
which drug concentrations have been determined over time over the course 
of several doses.  In this case, the data are expected to be fit by a 
saturable (Michaelis-Menton) process.  I can get the ode routine to run 
with only one, initial dose.  How can I modify the state at intermediate 
time points to reflect additional input functions?  My script follows, 
with the doses and times noted.
Thanks in advance.  Paul

# Script for running mixed order (Michaelis-Menton) fit of data

BB_sim1 <- read.table("BB_sim1.csv", sep=",", header=TRUE, na.strings=".")
Time <- BB_sim1$TIME
MM.1dose<-function(time, state, pars)
{
with(as.list(c(state,pars))
{
dA <- Vmax * CONC[1] /(Km + CONC)
return (list(c(dA)))
}
    )
}

name.column(BB_sim1)
Doses<-c(0.2, 1, 5)

#if(Time==0) Dose=Doses[1]
#if(Time==10 ) Dose=Doses[2]
#if(Time==25) Dose=Doses[3]

state <- c(CONC=CONC+Dose/V)
parms <- c (
    Vmax = 20
    Km = 2
    V = 0.07
    )

require(deSolve)
MM1.out <- as.data.frame(ode(state, Time, MM.1dose, parms))

ylim <- reange(c(MM1.out$Conc)
plot(MM1.out$Time, MM1.out$Conc, xlab="Time", ylab="Conc", type="1", 
ylim=ylim
-- 

Paul R. Hutson, Pharm.D.

Associate Professor

UW School of Pharmacy

777 Highland Avenue

Madison WI 53705-2222

Tel  608.263.2496

Fax 608.265.5421

Pager 608.265.7000, p7856