Development of a novel intestinal and vascular access port (IVAP) rabbit model to study regiospecific oral absorption pharmacokinetics

Background and Purpose: The limited availability and cost of many drugs pro hibits routine use of the previously developed intestinal and vascular acce ss port (IVAP) canine model by our group. A lower animal species model such as the rabbit is suitable for implanting intestinal and vascular access po rts for investigating regiospecific intestinal absorption and hepatic elimi nation while requiring significantly lower doses of drugs. In addition, exp ression of certain cytochrome P450 enzymes and apical secretory and absorpt ive transporters in rabbit intestine is similar to that in humans making th e rabbit a suitable model. Methods: Individual 5-F Silastic catheters were placed in the proximal or d istal portion of the small intestine or the colon of subject animals, while a 5-F Heparin Coated Polyurethane (HCP) catheter was implanted in the port al vein of each subject. The catheters were tunneled out of the abdomen and attached to separate subcutaneous access ports along the spine. The animal s were allowed a two-week minimum recovery period prior to being used in ph armacokinetic studies. Results and Discussion: After some initial difficulties, rabbits with IVAP implants proved to be an efficient and dependable model for investigating i ntestinal and hepatic extraction of drugs. Fluoroscopic visualization of in testinal and portal venous catheters indicated that surgically implanted ca theters did not interfere with gastrointestinal motility or blood flow into the liver, respectively. Acute pH studies in the proximal portion of the s mall intestine were consistent with normal GI motility patterns.