The beagle dog as a predictor of gastrointestinal findings in humans caused by the prostacyclin analogue taprostene.
Beagle dogs were exposed orally to the prostacyclin analogue taprostene for four weeks. Dose levels of 200-3000 micrograms/kg body weight/day were used. Specific activity of taprostene on the digestive system compared to other species is reported. It is characterized by hypermotility of the gastrointestinal tract resulting in intestinal invagination in some animals. Gastrointestinal symptoms occurred also after intravenous administration indicating a systemic stimulating effect on smooth muscles. Concerning reversible gastrointestinal side effects in humans after intravenous infusion of prostacyclin the results of this subacute toxicity study indicated that the dog is an adequate and sensitive species for preclinical testing of prostacyclins.
Wöhrmann
T
T
Department of Toxicology and Pathology, Gruenenthal Research Centre, Aachen, Germany.
Kögel
B Y
BY
Schneider
J
J
Matthiesen
T
T
D000818:Animals; D004064:Digestive System / Q000187:drug effects* / Q000473:pathology*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D011464:Epoprostenol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D005260:Female; D005544:Forecasting; D005767:Gastrointestinal Diseases / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D008297:Male
C039188:taprostene; D011464:Epoprostenol