An assessment of two gastric transport models currently used in safety pharmacology testing.
1. The potential effects of new drugs on the digestive system can be examined in a number of model systems of which intestinal motility in the mouse and/or gastric emptying in the rat are examples recommended for safety pharmacology evaluation. 2. Intestinal motility, assessed by the transit of carmine dye in the mouse and gastric motility, assessed by stomach weight in the rat, were examined using a range of clinical drugs or potent pharmacological agents known to affect gastrointestinal function. Assessment of both models in the guinea-pig was also evaluated. 3. Activity was demonstrated with codeine, diazepam, atropine and CCK-8 (all of which inhibited gastric function). However, neither model gave consistent and reliable results with the remaining reference compounds, namely metoclopramide, bethanechol, cisapride, deoxycholate, carbachol and domperidone. 4. In conclusion, this investigation questions the usefulness of simple models of gastrointestinal transport in the rodent as a means of detecting potential effects of a new drug on the digestive system. This finding should be of concern to the pharmaceutical industry as these simple models are routinely used as part of a regulatory safety pharmacology 'package' of studies.
Baldrick
P
P
Department of Toxicological Research, UCB SA, Braine-l' Alleud, Belgium.
Bamford
D G
DG
Tattersall
M L
ML
D000818:Animals; D005260:Female; D005746:Gastric Emptying / Q000187:drug effects*; D005769:Gastrointestinal Motility / Q000187:drug effects*; D006168:Guinea Pigs; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D010600:Pharmacology / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014116:Toxicology / Q000379:methods