Development of a Novel Intestinal and Vascular Access Port (IVAP) Rabbit Model to Study Regiospecific Oral Absorption Pharmacokinetics

• Published in: Comparative medicine Vol. 51; no. 4; pp. 349 - 356
• Main Authors: Kunta, Jeevan R., Perry, Barbara A., Sutyak, John P., Sinko, Patrick J.
• Format: Journal Article
• Language: English
• Published: United States American Association for Laboratory Animal Science 01.08.2001
• Subjects: active transport; Administration, Oral; animal models; Animals; blood supply; Catheterization, Peripheral; Catheterization, Peripheral - veterinary; Catheters, Indwelling; Catheters, Indwelling - veterinary; Coated Materials, Biocompatible; Colon; costs and returns; Dimethylpolysiloxanes; Female; Gastrointestinal Motility; halothane; Heparin; Hydrogen-Ion Concentration; Intestinal Absorption; Intestine, Small; isoflurane; laboratory animals; Liver; Liver - blood supply; liver function; metabolism; oral administration; Pharmacokinetics; Polyurethanes; portal vein; Portal Vein - surgery; rabbits; Rabbits - metabolism; Rabbits - surgery; Silicones; small intestine; Specific Pathogen-Free Organisms; surgery; veterinary
• ISSN: 1532-0820

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