Theophylline data set
The data considered here are courtesy of Dr. Robert A. Upton of the University of California, San Francisco. Theophylline is a methylxanthine drug used in therapy for respiratory diseases such as chronic obstructive pulmonary disease (COPD) and asthma under a variety of brand names. Theophylline was administered orally to 12 subjects whose serum concentrations were measured at 11 times over the next 25 hours. This is an example of a laboratory pharmacokinetic study characterized by many observations on a moderate number of individuals. The data set can be seen here, and the corresponding Datxplore project here (notice that both file should be in the same folder to be correctly linked). A representation of the concentration over time for each subject is presented on the following figure (notice, that this figure was generated using Datxplore).
The purpose of this page is to see the construction, the definition and the use of such a data set in Datxplore and Monolix. For sake of simplicity, we look only on one subject (corresponding to ID 1).
Simplified data set
The data set for subject one writes as follows
ID AMT TIME CONC WEIGHT SEX 1 4.02 0 . 79.6 M 1 . 0.25 2.84 79.6 M 1 . 0.57 6.57 79.6 M 1 . 1.12 10.5 79.6 M 1 . 2.02 9.66 79.6 M 1 . 3.82 8.58 79.6 M 1 . 5.1 8.36 79.6 M 1 . 7.03 7.47 79.6 M 1 . 9.05 6.89 79.6 M 1 . 12.12 5.94 79.6 M 1 . 24.37 3.28 79.6 M
One can see the following columns
- ID: the subject ID, column-type ID.
- AMT: the amount of drug provided to this subject, column-type AMOUNT.
- TIME: the time of the event, column-type TIME.
- CONC: the measured concentration, column-type OBSERVATION.
- WEIGHT: Weight of the subject, column-type CATEGORICAL COVARIATE.
- SEX: Sex of the subject, column-type CATEGORICAL COVARIATE.
Several points can be noticed.
- The first line corresponds to a dose, while the other ones are measurements. This explains the dot in the CONC column for the first line and the dots in the AMT column for the other ones.
- The covariates columns (the continuous WEIGHT and the categorical SEX) are constant over the individual. Even though it is not necessary, we encourage the user to fill the columns for readability and usage reasons.
- Finally, notice that no initial washout is needed at the beginning as by default, the null initial condition is used for parameter estimation.