Cannulated Conscious Rat Models

With this experimental set-up, absolute bioavailability and hepatic extraction ratio ( h) can be directly calculated as per Eqs. 2.32 and 2.33  

Using an alternative method, generally referred to as an indirect method, Eg may also be estimated following i.d. dosing alone and sampling portal blood and the systemic circulation concurrently. The mass of drug appearing in the portal vein (Ma) is defined as follows  

Ma may also be estimated from the absorption flux of drug in the portal vein as follows  

Direct determination of portal blood flow rate is difficult and would generally require placement of an electronic flow probe in each animal. However the technique proposed by Hoffman et al. utilised tritiated water as an absorption probe (i.e. internal standard) [89], By dosing and sampling drug/ absorption probe concurrently, factors such as variable portal blood flow rate are normalised between experiments. 

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