Prediction of blood drug concentration-time (C-t) profiles does not require a deconvolution step

If you are re-visiting this post, please make sure that you read the correction at the end of this post.

It appears that there is confusion that to develop IVIVC one is required first to de-convolute a plasma drug concentration-time (C-t) profile to obtain a so called “weighting function or factor” and then this function should be used to predict C-t profiles. The confusion appears to come from the way the concept and practice of IVIVC have been presented in literature.

As described in some earlier posts (link1, link2, link3, link4), and a publication (link), to develop or evaluate products one does not require IVIVC. The IVIVC is a step to relate in vitro dissolution to in vivo dissolution/absorption this is why one requires a de-convolution step to obtain in vivo dissolution from a C-t profile. However, it is very important to note that during the product development and evaluation stage one does not have C-t profiles, and the formulator is required to predict/estimate C-t profiles using experimentally observed in vitro dissolution results of test products. Therefore, at this stage the formulator cannot use the de-convolution step.

On the other hand, as stated above, at the product development stage, one needs to predict C-t profiles, for this purpose the only option is to use the convolution method. Mathematically to use the convolution method one would require a “weighting function or factor”, which in reality is the drug elimination rate equation, following drug administration using IV bolus. This weighting function or elimination rate equation can be obtained from literature. For most drugs, the elimination rate equation can easily be derived using the elimination half lives. Thus, there is no reason to conduct a bio-study to obtain this weighting function or elimination rate equation, as literature often suggests.

To conclude, for predicting C-t profiles one only requires a one step convolution method. The convolution method requires the use of a weighting function, which in reality is the elimination rate equation of the drugs, which can be obtained from literature. Combining the dissolution results with the elimination rate equation (weighting function) along with the volume of distribution and bioavailability values of the drug, also obtained from literature, and using the suggested spreadsheet software provide the required C-t profiles.

Note: Earlier it was stated that one obtains the “input function” from the deconvolution step. However, it was meant to be the “weighting function or factor” which one obtains from the deconvolution step. Therefore, accordingly, the wordings have been changed in the post. My apologies for this oversight (March 18, 2012).

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