Theoph data frame has 132 rows and 5 columns of data from
an experiment on the pharmacokinetics of theophylline.
This data frame contains the following columns:
a factor with levels
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 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.
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)
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"), 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 3.45e-07 *** lKa -0.18284 0.15145 -1.207 0.262 lCl -3.17016 0.08236 -38.493 2.28e-10 *** --- 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: 5.796e-06
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