Varga F, Fischer E, Szily T S
Pharmacology. 1975;13(5):401-8. doi: 10.1159/000136931.
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.
口服给药后，氯喹在大鼠中导致胃排空以及其自身从小肠吸收出现剂量相关的延迟。乙酰-β-甲基胆碱（0.75毫克/千克腹腔注射）对氯喹的腹腔半数致死量（102毫克/千克）没有显著影响，但将口服半数致死量从1080毫克/千克降至280毫克/千克。乙酰-β-甲基胆碱增加了胃排空速率以及小肠的推进运动。结果，与药物接触的肠黏膜表面积增大，导致氯喹吸收加快。以1毫克/分钟/千克的速率将氯喹输注到肠系膜静脉中，麻醉的大鼠可耐受数小时。然而，增加剂量会导致存活时间缩短并最终导致死亡。得出的结论是，胃排空可能在药物的肠道吸收速率和口服毒性中起重要作用。
