Assessment and validation of animal models to evaluate topical effects of substances on gastrointestinal mucosa.
The in situ rabbit colon model is a sensitive and reproducible test to evaluate the topical effect of up to three substances applied to the colonic mucosa. Vibra-Tabs (doxycycline hyclate), Inderal (propranolol hydrochloride), and Slow-K (potassium chloride) were compared for topical effects in the Carlborg-Densert cat esophagus model, the Alphin-Droppleman cat gastric mucosa model adapted for dog intestine, and the rabbit colon. Because results were comparable in all models, additional dosage formulations were subsequently tested only in the rabbit colon model. After exposure of the tissue to drugs, macroscopic and histologic effects were scored on four- and eight-point scales, respectively. In all three models, Vibra-Tabs and Inderal produced the highest macroscopic and histologic scores, although Slow-K was also irritating. In the rabbit colon model, potassium released from Slow-K and Micro-K Extencaps caused more irritation than from controlled-release GITS (KCl) (gastrointestinal therapeutic system KCl).
Fara
J W
JW
ALZA Corporation, Palo Alto, California 94303-0802.
Anderson
L D
LD
Casper
A G
AG
Myrback
R E
RE
D000818:Animals; D002415:Cats; D003106:Colon / Q000187:drug effects; D004285:Dogs; D004318:Doxycycline / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D004947:Esophagus / Q000187:drug effects; D005260:Female; D005753:Gastric Mucosa / Q000187:drug effects*; D007413:Intestinal Mucosa / Q000187:drug effects*; D007421:Intestine, Small / Q000187:drug effects; D007509:Irritants; D008297:Male; D008954:Models, Biological; D011189:Potassium Chloride / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits
D007509:Irritants; D011189:Potassium Chloride; D011433:Propranolol; D004318:Doxycycline