PK Data for Oral Dosing

This tutorial introduces the population pharmacokinetic modeling novice to the data format appropriate for most PK model fitting software systems with a focus on oral dosing data.

Introduction

We briefly describe a data format typically used in pharmacokinetics (PK) and pharmacodynamics (PD) modeling, especially relevant to our example oral dosing data. We describe the data form using data items required in NONMEM, which is acceptable in most PK software. More extensive description of data format appropriate for PK software can be found in the manual of each software such as the MONMEM manual\(^{1}\).

Population PK/PD Data Format

Here is an example of data for orally administered drugs in a suitable format for PK analysis using most PK software including NONMEM.

   id   time  amt   dv mdv evid addl II age
1   1    0.0 10.0   NA   1    1   27 12  46
2   1  336.0   NA 16.1   0    0   NA NA  46
3   1  336.5 10.0   NA   1    1  139 12  46
4   1 2015.0   NA  6.4   0    0   NA NA  46
5   1 2015.5  5.0   NA   1    1  105 12  46
6   1 3287.0   NA  5.6   0    0   NA NA  46
7   1 3287.5  5.0   NA   1    1  285 12  46
8   1 6720.0   NA  6.6   0    0   NA NA  46
9   1 6720.5  5.0   NA   1    1  265 12  46
10  1 9911.0   NA  5.0   0    0   NA NA  46
11  2    0.0 10.0   NA   1    1   27 12  72
12  2  336.0   NA 15.1   0    0   NA NA  72
13  2  336.5 10.0   NA   1    1   65 12  72
14  2 1128.0   NA 11.7   0    0   NA NA  72
15  2 1128.5  7.5   NA   1    1   25 12  72
16  2 1440.0   NA  2.9   0    0   NA NA  72
17  2 1440.5  2.5   NA   1    1   29 12  72
18  2 1800.0   NA  2.2   0    0   NA NA  72
19  2 1800.5  2.5   NA   1    1   29 12  72
20  2 2160.0   NA  4.3   0    0   NA NA  72
21  3    0.0  2.5   NA   1    1   27 12  56
22  3  336.0   NA  3.4   0    0   NA NA  56
23  3  336.5  2.5   NA   1    1  159 12  56
24  3 2256.0   NA 10.2   0    0   NA NA  56
25  3 2256.5  7.5   NA   1    1   17 12  56
26  3 2472.0   NA  7.5   0    0   NA NA  56

This simple example has two types of data rows, dose events (information concerning dosing) and concentration events (information concerning blood concentration levels for the drug of interest). The columns indicate the following information:

1. id: unique identifier for each individual in the dataset.
2. time: time of either dosing or concentration measurement.
3. amt: dose amount; NA for concentration events.
4. dv: drug blood concentration value, which is DV (dependent variable) as NONMEM data item; NA for a dose event.
5. mdv: missing dependent variable; 1 for indicating that there is no dependent variable (in this case, blood concentration), 0 for dependent variable.
6. evid: event ID; 1 for indicating dose event (amt, II, and addl for this record will be used for the drug dose information if evid = 1), 0 for observation (or dependent variable if mdv = 0).
7. addl: additional doses; the number of times for additional oral dose to be repeated, which is 1 less than total number of repeated (identical) doses.
8. II: interdose interval, the amount of time between each additional dose.
9. age: an example covariate; each column can have covariates - these can be time varying or fixed within individual.

Taking the first row as an example, which is a dose event, a dose of 10 mg is taken at time 0 then 27 additional doses (the same 10 mg) are taken every 12 hours (time can take any unit, or the same unit of time variable). If we calculate each of these 27 doses then we see that the final dose is given at time = 324, 12 hours before the measured concentration of 16.1 in row 2. Of course this same dosing information could be expressed in 28 rows, (10 mg at time 0, 10 mg at time 12, 10 mg at time 24, etc.) but this more compact form is preferable in the presence of a regular dosing interval.

This PK data form will be generated using Build-PK-Oral module (see Build-PK-Oral).

Note that additional data items such as cmt and ss need to be specified depending on dosing schedule or PK/PD models. See MONMEM manual\(^{1}\) for details on cmt specifying compartment number for dosing or an observation and ss indicating steady-state dosing.

References

1. Beal, S.L., Sheiner, L.B., Boeckmann, A.J. & Bauer, R.J. (Eds). NONMEM 7.5 users guides (1989–2020).