Vivo Approaches to Differentiate Between Intestinal and Hepatic First-Pass Metabolism

In Vivo Approaches to Differentiate Between Intestinal and Hepatic First-Pass Metabolism 

Another way to estimate presystemic metabolism in the gut wall is more amenable to routine clinical practice and involves drug administration via intravenous and oral routes. In addition to the assumptions outlined for anhepatic patients, this method assumes an average liver blood that does not change during treatment and uses a simple PBPK model to estimate Fg according to Equation 12.5  

With this method, Tateishi et al. estimated Fg of midazolam as 0.53 0.22, which is in good agreement with the anhepatic data [124]. 

The obvious clinical limitations in directly assessing gut wall metabolism in humans underline the importance of modeling approaches. These will be briefly reviewed in Section 12.4.3. 

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