Calculation of time above MIC [R for BE/BA]

Dear Aceto81!

» ...I'm struggling with the time above the MIC90 and %time above MIC90.
» Prats et al. came up with a time of 102.5 hours and 94.9% of total time in SS.

Looking at you data, this seems to be a reasonable value.

» I have no idea about how to find the 102.5 hours.
» I searched in the forum's archive, in the manual of WinNonLin, on the web, but couldn't find any references.

It's not implemented in WinNonlin; but I'm right now at a conference in London where one of the lecturers is Jason Chittenden of Pharsight - I will ask him.

I don't know any reference either - except one by Jerome Skelly of the FDA, maybe 20 years ago. Start searching with the term "occupany time" or just "occupancy".

» Maybe someone can give me some help?
» I'm routinely use R, but now I'm also using WinNonLin.

If the values fall below the MIC and come up again (like in your case) do a linear interpolation. An algorithm is like this:
• Run a loop through the sampling time points
• If two subsequent concentrations include the MIC and the second one is above, tag an "up" marker
• If two subsequent concentrations include the MIC and the second one is below, tag a "down" marker
• If two subsequent concentrations are >MIC add the time interval to a stack
• If two subsequent concentrations are <MIC goto next concentration
• For the "up" markers perform a linear interpolation to find out where the "line" intersects the MIC; subtract this time value from the next time point and add it to the stack
• For the "down" markers perform a linear interpolation to find out where the "line" intersects the MIC; add this time value to the last time point and add it to the stack
• Occupancy time = the value of the stack
I would use rather R than WinNonlin for that purpose, although it shouldn't be that difficult to set it up too.

I just made a unchecked hotel-room quickshot in R; 116.5 hr >0.517 ug/ml within 0 - 124 hr?!!

Dif-tor heh smusma 🖖
Helmut Schütz

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