Hello,
We will have IV infusion administration and would like to calculate PK parameters using non-compartmental analysis. The sponsor wants the clearance (CL) to be reported however in the help section, beside the CL formula “for extravascular administration” is mentioned.
Could you please suggest on reporting CL value after IV infusion.
Thank you,
Murat
I guess from your post you have not used WinNonlin’s NCA tool before as the dosing option for IV should be quite clear; I have highlighted it the screen shot below;
From your quote I guess you are looking at the table on page 46 of the Phoenix WinNonlin 6.4 User’s Guide.pdf, or a corresponding version; and I think it’s perhaps a little unclear. The formula for clearance is dose/AUC,
what the table is I think trying to draw you attention to is the footnote a. that can be seen on the next page explaining that CL_F is what you will get from Extravascular administration, where F is the fraction of dose absorbed, (and unknown if you only have Extravascular data).
In short you can go ahead and select the administered dose route and the NCA engine will use the correct formula automatically. However I am always cautious that not to recommend you just ‘push’ the button and It may well be worth you looking at our intro to WNL ;
http://certara.docebosaas.com/lms/index.php?r=course/details&id=26
and/or fundamentals of PK courses which are available online;
http://certara.docebosaas.com/lms/index.php?r=course/details&id=33
to have a better background in what you are doing and how to generate, interpret and present your results appropriately. We can also provide tailored onsite training, or you can join a public course;
Simon.
Dear Simon,
Thank you for your reply. I guess my question was not clear enough for you.
I will select IV infusion administration (intravascular), and want to know how to report CL in this model. Is it appropriate to report CL for intravascular models such as IV infusion? What is the formula? The formula you have mentioned seems to be for extravascular use only.
By the way I’m using Version 6.3. In the help section beside the formula there’s a footnote “a” however there’s no “a” at the bottom of the page and not in the next page. Instead there’s “1”. and footnote “1” says:
“For extravascular models (model 200), the fraction of dose absorbed cannot be estimated; therefore Volume and Clearance for these models are actually Volume/F or Clearance/F where F is the fraction of dose absorbed.”
Thank you.
Dear Murat, again, if you select the appropriate ‘Type’ in Dose Options, in this case IV infusion then the appropriate formula are already selected for you.
That Clearance = Dose/AUC is not something specifc to Phoenix WinNonlin. It is a standard assumption of NCA theory, for instance p24 of 3rd Ed Clinical Pharmacokinetics and Pharmacodynamics : Concepts and Applications by Rowland and Tozer that I happen to have on my desk at the moment.
Or https://www.boomer.org/c/p4/c20/c2001.html
or page 4 of http://www.agah.eu/fileadmin/_migrated/content_uploads/PK-glossary_PK_working_group_2004.pdf.
Simon.
