Effects of fasting on evaluation of gastrointestinal transit with charcoal meal.
BACKGROUND
At the present time, most studies investigating gastrointestinal transit time with charcoal are conducted in fasted rats. It seems reasonable to hypothesize that the fasting state of rats could influence the effect a compound had on gastrointestinal transit time. The purpose of this study was to investigate the effects of food on the pharmacological effects on gastrointestinal transit.


METHODS
For each drug investigated, two sets of 32 male Sprague-Dawley rats were used. One set was studied after being fasted for approximately 6 h, the second set was studied after free access to food. Each set had 4 groups of animals (n=8/group) that were administered different doses, allowing the assessment of the drug effect after fasting and after free access to food. Animals were administered 0, 10, 25, and 75 mg/kg of morphine; 0, 10, 20, and 40 mg/kg loperamide, or 0, 0.05, 0.5, and 3.0 mg/kg clonidine. At predetermined times, an activated charcoal suspension was administered by oral gavage. Thirty minutes after receiving the charcoal meal, rats were euthanized and the small intestine was removed. The length of the small intestine and the distance traveled by the charcoal were recorded. For each animal, gastrointestinal transit was calculated as the percentage of the distance traveled relative to the total length of the small intestine.


RESULTS
Baseline (vehicle dosed animals) gastrointestinal transit was significantly greater in fasted versus fed rats. In fasted rats, morphine did not have a significant effect on transit. In fed rats, 25 and 75 mg/kg morphine caused a significant decrease in transit. In fed and fasted rats, 0.5 and 3 mg/kg clonidine caused a significant decrease in transit. Loperamide did not affect gastrointestinal transit in fed or fasted rats at doses up to 40 mg/kg.


CONCLUSIONS
These data demonstrate that food does not reduce the sensitivity of the gastrointestinal transit time.
Mittelstadt
S W
SW
Drug Safety Assessment, Procter and Gamble Pharmaceuticals, Miami Valley Innovation Center, Cincinnati, OH 45252, USA. mittelstadt.sw@pg.com
Hemenway
C L
CL
Spruell
R D
RD
D000818:Animals; D002606:Charcoal / Q000008:administration & dosage; D003000:Clonidine / Q000009:adverse effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods*; D005215:Fasting / Q000502:physiology*; D005508:Food Deprivation; D005765:Gastrointestinal Agents / Q000009:adverse effects* / Q000145:classification; D005772:Gastrointestinal Transit / Q000187:drug effects / Q000502:physiology*; D008139:Loperamide / Q000009:adverse effects; D008297:Male; D009020:Morphine / Q000009:adverse effects; D009294:Narcotics / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D005765:Gastrointestinal Agents; D009294:Narcotics; D002606:Charcoal; D008139:Loperamide; D009020:Morphine; D003000:Clonidine