Effect of gastric emptying rate on the intestinal absorption of chloroquine in rats

Pharmacology
F VargaT S Szily

Abstract

After oral administration, chloroquine caused a dose-related delay in gastric emptying and in its own absorption from the small intestine in rats. Acetyl-beta-methylcholine (0.75 mg/kg i.p.) did not influence the intraperitoneal LD50 value of chloroquine (102 mg/kg) significantly, but reduced oral LD50 from 1,080 to 280 mg/kg. Acetyl-beta-methylcholine increased both the gastric emptying rate and the propulsion motility of the small intestine. As a consequence, the intestinal mucosal surface that had come into contact with the drug was increased in size, resulting in more rapid absorption of chloroquine. Infusion of chloroquine at a rate of 1 mg/min/kg into a mesenteric vein was tolerated by anaesthetized rats for hours. Increasing the dose, however, led to shorter survival times and eventually to death. It is concluded that gastric emptying may play an important role in the rate of intestinal absorption and in the oral toxicity of drugs.

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