Bioequivalence and Bioavailability Forum

Dear Ace!

❝ you did a hell of a job.

❝ Great thinking!

To be honest, it was more of try-and-error than thinking. Reading the online-help (and better: the User’s Guide) was just a little helpful. Only once I found out what WinNonlin was doing, I could understand the explanations – I’m getting old…

❝ Do you think that the log/linear approach for the descending part is better than the classic linear approach?

❝ As you already stated, the elimination phase is log/linear, so maybe this is more correct than the 'classic' approach.

Yes, I would think so – especially if time points are rather ‘far’ apart.

❝ Or maybe we can choose, as long as we clearly report which method we used?

According to WinNonlin’s User’s Guide (page 186, PDF page 204) both options should be possible to choose from; but whatever I tried always ended up lin/log…
Another nuisance: for MR formulations it would be nice to calculate the time interval, where C≥50%C_max (Half Value Duration, HVD) or C≥75%C_max (Plateau Time, t_75%). In the ‘Therapeutic response windows’ tab WinNonlin shows in one column individual’s C_max, but does not allow to enter a formula in the next column. So it's time for copy-and-paste…
For my two-segment absorption example it’s even worse: If I’m interested in the first and second part (like using WinNonlin’s partial area method) nothing helps but deleting the respective time points from the workbook.
If you just exclude them, WinNonlin will still present the global C_max only.

Yesterday I downloaded Phoenix WinNonlin 6 ‘beta’ and will have a look how they ‘do’ it there. I didn’t dare to install the 156MB yet (really lots of stuff: needs M$ Visual C++ compiler and Office 2003, includes all successors of the recent version: WinNonlin, WinNonMix, IVIVC Toolkit, a new graphical engine [yes, two independent y-axes, Trellis plots!], a graphical model builder [similar to KINETICA], and, and…).

❝ PS: anyone interested in the full R code with an extension to choose log or not?

Yes, me.
I gave it a short try with a start time = 0, and got the index error again. If you go with a log-version you probably must add small dummy concentrations for values below the LLOQ.