saemix (version 0.96.1)

theo.saemix: Pharmacokinetics of theophylline, in SAEM format

Description

The theo.saemix data frame has 132 rows and 6 columns of data from an experiment on the pharmacokinetics of theophylline. A column with gender was added to the original data for demo purposes, and contains simulated data.

Usage

theo.saemix

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. In the present package npde, we removed the data at time 0.

These data are analyzed in Davidian and Giltinan (1995) and Pinheiro and Bates (2000) using a two-compartment open pharmacokinetic model. These data are also available in the library datasets under the name Theoph in a slightly modified format and including the data at time 0.

Examples

data(theo.saemix)
saemix.data<-saemixData(name.data=theo.saemix,header=TRUE,sep="",na=NA, 
  name.group=c("Id"),name.predictors=c("Dose","Time"),
  name.response=c("Concentration"),name.covariates=c("Weight","Sex"),
  units=list(x="hr",y="mg/L",covariates=c("kg","-")), name.X="Time")

model1cpt<-function(psi,id,xidep) { 
	  dose<-xidep[,1]
	  tim<-xidep[,2]  
	  ka<-psi[id,1]
	  V<-psi[id,2]
	  CL<-psi[id,3]
	  k<-CL/V
	  ypred<-dose*ka/(V*(ka-k))*(exp(-k*tim)-exp(-ka*tim))
	  return(ypred)
}
# Default model, no covariate
saemix.model<-saemixModel(model=model1cpt,
  description="One-compartment model with first-order absorption",
  psi0=matrix(c(1.,20,0.5,0.1,0,-0.01),ncol=3,byrow=TRUE, 
  dimnames=list(NULL, c("ka","V","CL"))),transform.par=c(1,1,1))

# Note: remove the options save=FALSE and save.graphs=FALSE 
# to save the results and graphs
saemix.options<-list(seed=632545,save=FALSE,save.graphs=FALSE)

saemix.fit<-saemix(saemix.model,saemix.data,saemix.options)

# Model with covariates
saemix.model<-saemixModel(model=model1cpt,
  description="One-compartment model with first-order absorption",
  psi0=matrix(c(1.,20,0.5,0.1,0,-0.01),ncol=3,byrow=TRUE, 
  dimnames=list(NULL, c("ka","V","CL"))),transform.par=c(1,1,1), 
  covariate.model=matrix(c(0,0,1,0,0,0),ncol=3,byrow=TRUE),fixed.estim=c(1,1,1),
  covariance.model=matrix(c(1,0,0,0,1,1,0,1,1),ncol=3,byrow=TRUE),
  omega.init=matrix(c(1,0,0,0,1,0,0,0,1),ncol=3,byrow=TRUE),error.model="combined")

saemix.options<-list(seed=39546,save=FALSE,save.graphs=FALSE)

saemix.fit<-saemix(saemix.model,saemix.data,saemix.options)