theo.saemix: Pharmacokinetics of theophylline, in SAEM format

In belhal/saemix: Stochastic Approximation Expectation Maximization (SAEM) Algorithm

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

Format

This data frame contains the following columns:

Id:

an ordered factor with levels 1, ..., 12 identifying the subject on whom the observation was made. The ordering is by Time at which the observation was made.

Dose:

dose of theophylline administered orally to the subject (mg/kg).

Time:

time since drug administration when the sample was drawn (hr).

Concentration:

theophylline concentration in the sample (mg/L).

Weight:

weight of the subject (kg).

Sex:

gender of the subject (0=men, 1=women).

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.

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)

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)

# Not run (strict time constraints for CRAN)
# 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)

# Not run (strict time constraints for CRAN)
# saemix.fit<-saemix(saemix.model,saemix.data,saemix.options)

belhal/saemix documentation built on Sept. 10, 2019, 8:07 a.m.