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

It appears that there is confusion that to develop IVIVC, one is required first to de-convolute a blood drug concentration-time (C-t) profile to obtain a so-called “input function,” 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 the 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, one needs to predict C-t profiles at the product development stage. For this purpose, the only option is to use the convolution method. Mathematically to use the convolution method, one would require an “input function”, which in reality is the drug elimination rate equation, following drug administration using IV bolus. This input function or elimination rate equation can be obtained from the 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 input 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 an input function, which in reality is the elimination rate equation of the drugs, which can be obtained from the literature. Combining the dissolution results with the elimination rate equation (input function) along with the volume of distribution and bioavailability values of the drug, also obtained from literature, and using the suggested Excel spreadsheet software provide the required C-t profiles.

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