Effects of Isoflurane on gastrointestinal motility after brief exposure in rats

In pre-clinical studies, investigation of oral formulations often necessitates the use of general anesthesia to facilitate deposition of material directly into the stomach. Since the effectiveness of intestinal drug absorption is dependent on gastric emptying (GE) and intestinal motility, drugs that influence either will also influence drug absorption. This study investigated gastrointestinal motility in rats after brief exposure to Isoflurane (ISO) general anesthesia for orogastric gavage. The use of metochlopramide was also evaluated. Twenty-five fasted rats were induced with brief ISO anesthesia (< 6 min). Rats were gavaged a gelatin capsule (8 mm (L) x 2.0 mm (o.d.)) containing 9 mg of activated charcoal powder (gastrointestinal marker) and rapidly recovered. Gavage was performed using a 15 cm feeding device with a soft hollow tip to hold the capsule. Study included three groups (60 and 120 min recovery. metochlopramide pre-treatment with 60 min recovery) and control. Animals were sacrificed for exposure and examination of the gastrointestinal tract following the allocated recovery period. Gastrointestinal transit of charcoal was reduced approximately 50% 120 min after brief ISO anesthesia. Metochlopramide pre-treatment did not increase gastrointestinal propulsion despite increased GE. These data warrant consideration in intestinal drug absorption studies where ISO is the anesthetic of choice. (c) 2005 Published by Elsevier B.V.