nlmeODE (version 0.2-1)

TheophODE: Pharmacokinetics of theophylline

Description

The TheophODE data frame has 132 rows and 6 columns of data from an experiment on the pharmacokinetics of theophylline.

Usage

data(TheophODE)

source

Boeckmann, A. J., Sheiner, L. B. and Beal, S. L. (1994), NONMEM Users Guide: Part V, NONMEM Project Group, University of California, San Francisco. Davidian, M. and Giltinan, D. M. (1995) Nonlinear Models for Repeated Measurement Data, Chapman & Hall (section 5.5, p. 145 and section 6.6, p. 176) Pinheiro, J. C. and Bates, D. M. (2000) Mixed-effects Models in S and S-PLUS, Springer (Appendix A.29)

Details

Boeckmann, Sheiner and Beal (1994) report data from a study by Dr. Robert Upton of the kinetics of the anti-asthmatic drug theophylline. Twelve subjects were given oral doses of theophylline then serum concentrations were measured at 11 time points over the next 25 hours. These data are analyzed in Davidian and Giltinan (1995) and Pinheiro and Bates (2000) using a two-compartment open pharmacokinetic model, for which a self-starting model function, SSfol, is available.

Examples

data(TheophODE)

OneComp <- list(DiffEq=list(               #Differential equations
                    dy1dt = ~ -ka*y1 ,        #Compartment 1
                    dy2dt = ~ ka*y1-ke*y2),   #Compartment 2
                ObsEq=list(                #Observation equation  
                    c1 = ~ 0,
                    c2 = ~ y2/CL*ke),
                Parms=c("ka","ke","CL"),   #Parameter names
                LogParms=TRUE,             #Estimate the logarithm of the parameters 
                States=c("y1","y2"),       #The names of the states in the sequence of DiffEq
                Init=list(0,0),               #Estimate the Initial states  
                JAC=TRUE,                  #Use the Jacobian             
                SEQ=FALSE)                 #Use sensitivity equations   

TheophModel <- nlmeODE(OneComp,TheophODE)

Theoph.nlme <- nlme(conc ~ TheophModel(ka,ke,CL,Time,Subject),
   data = TheophODE, fixed=ka+ke+CL~1, random = pdDiag(ka+CL~1), 
   start=c(ka=0.5,ke=-2.5,CL=-3.2),
   control=list(returnObject=TRUE,msVerbose=TRUE,tolerance=1e-3,pnlsTol=1e-1,msTol=1e-3))

plot(augPred(Theoph.nlme,level=0:1))