TivatrainerX: validation Remifentanil Kim-Obara-Egan

Disposition of Remifentanil in Obesity
A New Pharmacokinetic Model Incorporating the Influence of Body Mass
Tae Kyun Kim, M.D., Shinju Obara, M.D., Talmage D. Egan, M.D., and the Remifentanil Pharmacokinetics in Obesity Investigators
(Anesthesiology 2017; 126:1019-32)

When a pharmacokinetic or pharmacodynamic model is implemented in simulation software like TivatrainerX it is obvious that the implementation and simulation must be checked on correctness. This is what this blog is about.

TivatrainerX implementation of the Remifentanil Kim-Obara-Egan model, validated by graphical superposition.

See: https://blog.eurosiva.eu/pharmacokinetics-diy-part-1/ for a more detailed explanation of the technique.

Data were exported from TivatrainerX as CSV files using the improved export function in TivatrainerX. After importing these files in Numbers and adjusting axis graphs were constructed and compared with the published figures.

Screen copy of figure 6A overlayed with TivatrainerX simulation in red
Screen copy of figure 6B overlayed with TivatrainerX simulation in red

TivatrainerX simulation shows a perfect fit with figure 6 in the publication. Proofing correct implementation of the Pk parameters for male patients with different weight,height and age.

Misfit of both Euler(Numerical) and TivatrainerX with figure 7 when starting at T=0
Correct fit when starting at T=1min with Euler
Kim_Obara_Egan Remifentanil - Google Drive

Spreadsheet with numerical calculations and adjustable interval

A misfit was noted when TivatrainerX output was compared with Figure 7 in the publication. To make sure that the TivatrainerX algorithmes were correct the simulations were recalculated with Eulers numerical approach using Numbers spreadsheet. This spreadsheet is also exported to Google Drive so you can have a look. There were no differences between Euler and TivatrainerX. The misfit was resolved by starting the simulation at T=1 min instead of T=0. The authors confirmed that this is an unexpected behaviour of the simulation program they used. With TivatrainerX starting at T=1 min, a couple of curves were then compared:

with excellent results.


How to copy/paste in Tivatrainer and export data for use in a spreadsheet

The video shows how easy it is to export the simulation data after saving the file. The usual iPhone share function wil allow you save these data to files with apropriate format.

By using the Fat Free Mass(FFM) in the Pk parameters, the model is also gender dependent. All simulations above are done with a male subject and there is no example of a female subject. Therefore the FFM calculation was compared with the calculation in the original article(Janmahasatian S, Duffull SB, Ash S, Ward LC, Byrne NM, Green
B: Quantification of lean bodyweight. Clin Pharmacokinet
2005; 44:1051–65)


The Kim-Obara-Egan model is correctly implemented in TivatrainerX.