There is a short discussion of the above poster on the LearnPKPD blog;http://learnpkpd.com...e-tip-for-pkpd/
together with a workaround tip if your custom model ever freezes.
I'd invite any readers to let us know of other publications using the IVIVC toolkit so we can add to the library of
Tips for custom IVIVC models in Phoenix
February 18, 2016 By Bayo Olowoyeye 2 Comments
Author: Simon Davis
Original Poster Link
The IVIVC tool within Phoenix is a convenient and powerful tool to build an in vivo-invitro correlation model using dissolution experiments and real in vivo profiles. This module can support your organisation in formulation development and even in applying for Biowaivers.
The tool has a flexible library of built-in models that can be modified to better fit more complicated, non-linear relationships as demonstated in the attached AAPS poster presentation.
To briefly summarise the problem was to develop an In Vitro / In Vivo Correlation (IVIVC) model for a compound whose release rate specific bioavailability would not initially seem to support an IVIVC.
The formulation under evaluation is a capsule containing four different types of delayed release beads. Each bead is are characterized by a mean dissolution time (MDT) and a time lag (Tlag) and each of the seven formulations under study is comprised of a different ratio of each bead type.
Mean plasma profiles for 4 formulations (10-20 subjects per formulation) were deconvolved using the PK parameters that would relate to the intravenous kinetics of the compound. The generated series of fraction absorbed (Fabs) profiles were then overlaid with the dissolution profiles. Reviewing this plot suggested that the slower formulations had greater bioavailability than the fastest release (CR01) and the slower the release -the greater the bioavailability.
This meant that a simple library model could not describe the data well. Since the Levy plot indicated two time scales a bi-linear model was proposed where an initial lag (TL1) to be consistent with a stomach emptying effect together with a Tcut representing intestinal transit time switching between phases.
In this case reviewing the original exploratory plots together with the diagnostic plots an initial library model was refined to consider some physiological mechanismse.g. first pass metabolism greatest in the small intestine, thereby creating an acceptable custom IVIVC model.
However occasionally when running a custom model you may find that IVIVC model the object freezes (you can tell when this has happened because the status bar fails to advance)
Should this happen
CTRL+SHIFT+Escape to bring up Windows Task Manager
Navigate to the Processes tab.
Try ending the wnlpk32.exe process
It should automatically restart and then complete without error
Take it as a reminder to save you Phoenix project!
Edited by Simon Davis, 15 July 2020 - 02:16 PM.