Pharmacokinetic modelling of Indomethacin using differential equations

Description

The Indometh data frame has 66 rows and 3 columns of data on the pharmacokinetics of indomethacin.

Format

The Indometh data frame contains the following columns:

Subject

an ordered factor with containing the subject codes. The ordering is according to increasing maximum response.

time

a numeric vector of times at which blood samples were drawn (hr).

conc

a numeric vector of plasma concentrations of indomethacin (mcg/ml).

Details

Each of the six subjects were given an intravenous injection of indomethacin.

Source

Kwan, Breault, Umbenhauer, McMahon and Duggan (1976), ``Kinetics of Indomethacin absorption, elimination, and enterohepatic circulation in man'', Journal of Pharmacokinetics and Biopharmaceutics, 4, 255-280.

Davidian, M. and Giltinan, D. M. (1995) Nonlinear Models for Repeated Measurement Data, Chapman & Hall (section 5.2.4, p. 134)

Pinheiro, J. C. and Bates, D. M. (2000) Mixed-effects Models in S and S-PLUS, Springer.

See Also

Indometh, SSbiexp

Examples

data(Indometh)

TwoComp <- list(DiffEq=list(                         
                    dy1dt = ~ -(k12+k10)*y1+k21*y2 , 
                    dy2dt = ~ -k21*y2 + k12*y1),     
                ObsEq=list(                          
                    c1 = ~ y1,                       
                    c2 = ~ 0),                       
                States=c("y1","y2"),                 
                Parms=c("k12","k21","k10","start"),  
                Init=list("start",0))

IndomethModel <- nlmeODE(TwoComp,Indometh)

#Remove '#' below to run the estimation

#Indometh.nlme <- nlme(conc ~ IndomethModel(k12,k21,k10,start,time,Subject),
#   data = Indometh, fixed=k12+k21+k10+start~1, random = pdDiag(start+k12+k10~1), 
#   start=c(k12=-0.05,k21=-0.15,k10=-0.10,start=0.70),
#   control=list(msVerbose=TRUE,tolerance=1e-1,pnlsTol=1e-1,msTol=1e-1),
#   verbose=TRUE)

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