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IVIVC Toolkit™ for WinNonlin® — Features

The IVIVC Toolkit for WinNonlin offers several tools that enable the user to do in vivo-in vitro correlation modeling in WinNonlin.

IVIVC Wizard

The IVIVC Wizard manages the multitude of data in a two-stage IVIVC workflow and helps the user stay on top of the process.  After mapping the dissolution and study data, the IVIVC Wizard automates several steps of the process, including:

  • Fitting Unit Impulse Responses (UIRs) for each study subject
  • Smoothing dissolution data
  • Deconvolving the absorption profiles for each formulation and subject
  • Fitting the IVIVC model
  • Evaluating the IVIVC model
  • Predicting response to test formulations

In addition, the IVIVC Wizard helps the user manage the IVIVC process by providing:

  • A panel of intelligent status indicators, which indicate if a step is completed or needs to be refreshed
  • A convenient IVIVC project workspace to keep track of data and project status
  • One-click "refresh" the analysis

Users will appreciate the many options that the IVIVC Wizard provides:

Fitting UIRs

  • Use intra-venous (IV), immediate release (IR), or any other polyexponential data for UIR
  • Automatic, per-subject selection of number of compartments
  • Stripping absorption constant, to get IV PK from IR dosing
  • Fit with or without lag-time
  • Multiple weighting/residual variance options

Dissolution Smoothing

  • Smooth using sigmoid models
  • Fix parameters in estimation
  • Multiple weighting/residual variance options

IVIVC Modeling

  • Simple time-scaled linear models
  • User specified, custom models

Evaluating Correlation and Prediction

  • Choose geometric or arithmetic mean for summarizing PK data
  • Select AUC type and calculation method

A la Carte Tools

The IVIVC Toolkit also contains several tools that, in conjunction with some of the tools included in the base WinNonlin, enable the user to work through the process of developing an in vivo-in vitro correlation.

Deconvolution

Deconvolution is the process whereby, with defined pharmacokinetics, one can impute the necessary drug input rate that gives an observed plasma profile.  The enhancements to the Deconvolution tool in the latest version of WinNonlin enable the user to deconvolve individual subjects using their unique pharmacokinetic profiles.  Methods available for deconvolution include: Wagner-Nelson, Loo-Riegelman, and numerical deconvolution.

Convolution

Convolution is the reverse process of deconvolution.  Given a UIR function and a known input profile (e.g. absorption), convolution finds the response to the input. The Convolution tool in the IVIVC Toolkit will compute any number of output profiles from a collection UIR functions combined with any number of inputs.

Levy Plot

A Levy Plot is an analysis chart that maps the in vitro dissolution and in vivo absorption times by fraction dissolved.  That is, this plot compares the time to a certain fraction dissolved between the in vivo and in vitro experiments.  A Levy Plot allows one to assess the time scale and shift differences between in vitro dissolution and in vivo absorption, and quickly determine if a correlation could be achievable.