Pharmacokinetics of Theophylline

The Theoph data frame has 132 rows and 5 columns of data from an experiment on the pharmacokinetics of theophylline.

Usage

Theoph

Format

An object of class c("nfnGroupedData", "nfGroupedData", "groupedData", "data.frame") containing the following columns:

Subject

an ordered factor with levels 1, ..., 12 identifying the subject on whom the observation was made. The ordering is by increasing maximum concentration of theophylline observed.

Wt

weight of the subject (kg).

Dose

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

Time

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

conc

theophylline concentration in the sample (mg/L).

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.

This dataset was originally part of package nlme, and that has methods (including for [, as.data.frame, plot and print) for its grouped-data classes.

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)

See Also

SSfol

Examples

require(stats); require(graphics)

coplot(conc ~ Time | Subject, data = Theoph, show.given = FALSE)
Theoph.4 <- subset(Theoph, Subject == 4)
fm1 <- nls(conc ~ SSfol(Dose, Time, lKe, lKa, lCl),
           data = Theoph.4)
summary(fm1)
plot(conc ~ Time, data = Theoph.4,
     xlab = "Time since drug administration (hr)",
     ylab = "Theophylline concentration (mg/L)",
     main = "Observed concentrations and fitted model",
     sub  = "Theophylline data - Subject 4 only",
     las = 1, col = 4)
xvals <- seq(0, par("usr")[2], length.out = 55)
lines(xvals, predict(fm1, newdata = list(Time = xvals)),
      col = 4)