Pharmacokinetics of theophylline

Description

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

Usage

Theoph

Format

This data frame contains the following columns:

Subject

a factor with levels A, ..., L identifying the subject on whom the observation was made.

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.

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(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)

Results

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> library(MEMSS)
Loading required package: lme4
Loading required package: Matrix

Attaching package: 'MEMSS'

The following objects are masked from 'package:datasets':

    CO2, Orange, Theoph

> png(filename="/home/ddbj/snapshot/RGM3/R_CC/result/MEMSS/Theoph.Rd_%03d_medium.png", width=480, height=480)
> ### Name: Theoph
> ### Title: Pharmacokinetics of theophylline
> ### Aliases: Theoph
> ### Keywords: datasets
> 
> ### ** Examples
> 
> require(lattice)
Loading required package: 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)

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

> 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)
> 
> 
> 
> 
> 
> dev.off()
null device 
          1 
>