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An assessment of two gastric transport models currently used in safety pharmacology testing

Department of Toxicological Research, UCB SA, Pharma Sector, Chemin du Foriest, B-1420 Braine-l' Alleud, Belgium

D G Bamford

Department of Drug Safety, Rhône-Poulenc Rorer, 6 Weldon Road, Loughborough, Leicestershire LE11 5RA, UK

M L Tattersall

Department of Safety Evaluation, Rhône-Poulenc Rorer, Summerpool Road, Loughborough, Leicestershire LE11 5DY, UK

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, cisa-pride, 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.

Key Words: gastrointestinal motility • gastric emptying • safety pharmacology • mouse • rat • guinea-pig

Human & Experimental Toxicology, Vol. 17, No. 1, 1-7 (1998)
DOI: 10.1177/096032719801700101


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