Bioequivalence and Bioavailability Forum

Dear Ramesh!

❝ Can anyone pls explain how to do Level C Correlation (IVIVC) by winnonlin with example.

Level C is a point-to-point relationship between an in vitro parameter (e.g., t_50%) and an in vivo metric (e.g., t_max, C_max, AUC).

In WinNonlin set up a workbook with two columns. In the first the dissolution (in vitro) parameter and in the second the PK metric (in vivo). You will need at least three formulations to set up a linear Level C and four formulations for a quadratic Level C. Values of the formulations go into the rows of the workbook. Send the data to a linear model; either Model 502 (Linear) or Model 503 (Quadratic). It’s possible to get a negative intercept – that’s an indication of a lag-time.
If you want to predict in vivo response from in vitro data (X) calculate it with the Final Parameters of the results workbook as:
Model 502: INT + SLOPE * X
Model 503: A0 + A1 + A2 * X

For an overview see

Cardot J-M, Beyssac E, and M Alric
In Vitro–In Vivo Correlation: Importance of Dissolution in IVIVC
Dissolution Technologies 14(1), 15–9 (2007)
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