A Chronic Bile Duct and Intravenous Cannulation Model in Conscious Rabbits for Pharmacokinetic Studies

In the development of novel pharmaceutical compounds, pharmacokinetic parameters, such as the extent of biliary excretion, must be characterized. Pharmacokinetic studies in nonrodent species, typically dogs, are generally required for new drug approvals. However, in some cases, rabbits may be a more desirable model. We developed a surgical procedure for the intermittent or continuous collection of bile for long-term use. This surgery involves the removal of the gallbladder and cannulation of the proximal and distal aspects of the common bile duct using a 40 cm flexible surgical-grade cannula. The cannula loop is passed subcutaneously and exteriorized between the scapulae to divert bile flow. During use, the proximal cannula segment is attached to a collection container placed in a nylon torso jacket worn by the animal, and the distal segment of catheter is sealed with a stainless-steel adapter. An auricular catheter, secured by ligatures, is placed aseptically into the lateral ear vein and the tip is advanced to the cranial vena cava for serial blood collection. Daily infusions of a heparinized saline "lock" ensure patency. These procedures have been used in 18 rabbits for up to 1 month without clinical complications. Complete blood counts, biochemical profiles, body weights, and bile flow were monitored weekly and reflected normal enterohepatic circulation.