Description Usage Format Details Source See Also Examples
The Theoph
data frame has 132 rows and 5 columns of data from
an experiment on the pharmacokinetics of theophylline.
1 
This data frame contains the following columns:
a factor with levels A
, ..., L
identifying the
subject on whom the observation was made.
weight of the subject (kg).
dose of theophylline administered orally to the subject (mg/kg).
time since drug administration when the sample was drawn (hr).
theophylline concentration in the sample (mg/L).
Boeckmann, Sheiner and Beal (1994) report data from a study by Dr. Robert Upton of the kinetics of the antiasthmatic 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 twocompartment open pharmacokinetic model,
for which a selfstarting model function, SSfol
, is available.
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) Mixedeffects Models in S and SPLUS, Springer (Appendix A.29)
1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17  require(lattice)
xyplot(conc ~ Time  Subject, Theoph, aspect = 'xy',
xlab = "Time since drug administration (hr)",
ylab = "Theophylline concentration (mg/L)")
Theoph.D < subset(Theoph, Subject == "D")
fm1 < nls(conc ~ SSfol(Dose, Time, lKe, lKa, lCl),
data = Theoph.D)
summary(fm1)
plot(conc ~ Time, data = Theoph.D,
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], len = 55)
lines(xvals, predict(fm1, newdata = list(Time = xvals)),
col = 4)

Loading required package: lme4
Loading required package: Matrix
Attaching package: 'MEMSS'
The following objects are masked from 'package:datasets':
CO2, Orange, Theoph
Loading required package: lattice
Formula: conc ~ SSfol(Dose, Time, lKe, lKa, lCl)
Parameters:
Estimate Std. Error t value Pr(>t)
lKe 2.24833 0.14775 15.217 3.45e07 ***
lKa 0.18284 0.15145 1.207 0.262
lCl 3.17016 0.08236 38.493 2.28e10 ***

Signif. codes: 0 '***' 0.001 '**' 0.01 '*' 0.05 '.' 0.1 ' ' 1
Residual standard error: 0.5926 on 8 degrees of freedom
Number of iterations to convergence: 5
Achieved convergence tolerance: 5.796e06
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