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