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


CONCLUSIONS
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.
Kunta
J R
JR
Department of Pharmaceutics, College of Pharmacy, The State University of New Jersey Rutgers, Piscataway 08854, USA.
Perry
B A
BA
Sutyak
J P
JP
Sinko
P J
PJ
D000284:Administration, Oral; D000818:Animals; D002406:Catheterization, Peripheral / Q000662:veterinary*; D002408:Catheters, Indwelling / Q000662:veterinary*; D020099:Coated Materials, Biocompatible; D003106:Colon; D004129:Dimethylpolysiloxanes; D005260:Female; D005769:Gastrointestinal Motility; D006493:Heparin; D006863:Hydrogen-Ion Concentration; D007408:Intestinal Absorption; D007421:Intestine, Small; D008099:Liver / Q000098:blood supply; D010599:Pharmacokinetics; D011140:Polyurethanes; D011169:Portal Vein / Q000601:surgery*; D011817:Rabbits / Q000378:metabolism / Q000601:surgery*; D012828:Silicones; D013047:Specific Pathogen-Free Organisms
D020099:Coated Materials, Biocompatible; D004129:Dimethylpolysiloxanes; D011140:Polyurethanes; D012828:Silicones; C013830:baysilon; D006493:Heparin