THE EFFECT OF SKF 525A ON THE DISTRIBUTION OF CARBON TETRACHLORIDE IN RATS

¹ Department of Pharmacology, Faculty of Medicine, University of Montreal, Montreal, Quebec, Canada

Rats were pretreated with SKF 525A, 40 mg/kg i. p., and gavaged 40 minutes later with C¹⁴Cl₄, 2 nil/kg (0.1 mc/kg). In rats sacrificed , 1 and 2 hours after C¹⁴Cl₄ administration, there was significantly less toluene-soluble C¹⁴ in the blood, liver, brain, muscle and fatty tissue of rats pretreated with SKF 525A. No significant difference was observed 5 hours after gavage and an increase in tissue C¹⁴ was found 12 hours after gavage in rats pretreated with SKF 525A. During the first six hours that followed C¹⁴Cl₄ gavage, rats pretreated with SKF 525A excreted less toluene-soluble C¹⁴ through the lungs. When the pretreatment was performed 66 hours before administration of C¹⁴Cl₄, there was a significant increase in blood C¹⁴Cl₄ of pretreated rats. When CCl₄ was administered i.p. or s.c., SKF 525A had no apparent effect on CCl₄ distribution in rats sacrificed one hour after C¹⁴Cl₄ administration. These results suggest that SKF 525A has a diphasic effect on the concentration of CCl₄ in tissues, which is probably due to an effect on the gastrointestinal absorption of CCl₄. This effect of SKF 525A could be a partial explanation for its protective effect on CCl₄ toxicity.