Hepatic portal vein cannulation

The use of hepatic portal vein-cannulated animals can be helpful in determining specific causes of poor bioavailability. After oral dosing, the total bioavailability of a compound is normally calculated as  

These multiple input experiments can be carried out in a crossover fashion. 

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Fill a cannula (Note 1) with heparin (1000 U/mL) and cannulate the hepatic portal vein about 1 inch below the point of branching into liver. Ease the cannula up to the point of branching and secure in place using the two threads, making sure that the knots are well away from the tapered tip of the cannula. If the cannulation is successful, blood will back-fill the cannula. 

Sable-Amplis, R., Abadie, D. Permanent cannulation of the hepatic portal vein in rats. J. Appl. Physiol. 1975, 38, 358-359. 

A second in vivo model system that is very useful in sorting through problems of low oral bioavailability is portal vein cannulated animals. There are two ways this experiment can be conducted to determine hepatic extraction (1) measure systemic plasma concentration after oral, portal vein, and systemic administration and (2) measure portal vein and hepatic vein concentrations after an oral dose. Both methods yield information on hepatic extraction and the percentage of dose reaching the portal circulation (the product of the fraction absorbed and the fraction metabolized by the gut wall). 

The estimation of in vivo hepatic CL requires cannulation of the portal vein. By comparing AUC of portal vein dosing and systemic dosing, CLh can be estimated with the following equations ... 

Murakami, T., et al. Separate assessment of intestinal and hepatic first-pass effects using a rat model with double cannulation of the portal and jugular veins. Drug Metab. Pharmacokinet. 2003, 18, 252-260. 

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