Hunter A L, Klaassen C D
Drug Metab Dispos. 1975 Nov-Dec;3(6):530-5.
The 24-hr LD50 of colchicine in newborn rats is 0.24 mg/kg, which is about 1/10 that observed in the adult. The 24-hr LD50 of colchicine was relatively constant in rats over 25 days of age. In an attempt to determine the mechanism of the increased sensitivity of the newborn rat to the toxic action of colchicine, the distribution of 3H after the administration of 3H-colchicine (0.1 mg/kg) was measured in 10- and 35-day-old rats. The concentration of 3H was higher in all tissues of the newborn than the adult after ip administration, suggesting an immaturity in the pathway for colchicine elimination. After iv administration, radioactivity disappeared much more slowly from the plasma of the newborn rat than from the adult. This was due to a lower capacity of the liver of the newborn to concentrate colchicine and to excrete it into the bile. Development of the hepatic excretory mechanism responsible for excretion of colchicine occurred at the same age as did the increase in LD50. These results suggest that colchicine is more toxic in the newborn because the drug remains in the body for a longer time due to immaturity of the liver excretory process.
秋水仙碱在新生大鼠中的24小时半数致死剂量（LD50）为0.24毫克/千克，约为成年大鼠的1/10。秋水仙碱在25日龄以上大鼠中的24小时LD50相对恒定。为了确定新生大鼠对秋水仙碱毒性作用敏感性增加的机制，对10日龄和35日龄大鼠注射3H-秋水仙碱（0.1毫克/千克）后测量了3H的分布。腹腔注射后，新生大鼠所有组织中的3H浓度均高于成年大鼠，这表明秋水仙碱消除途径不成熟。静脉注射后，新生大鼠血浆中的放射性消失速度比成年大鼠慢得多。这是因为新生大鼠肝脏浓缩秋水仙碱并将其排泄到胆汁中的能力较低。负责秋水仙碱排泄的肝脏排泄机制的发育与LD50的增加发生在相同年龄。这些结果表明，秋水仙碱在新生大鼠中毒性更大，因为由于肝脏排泄过程不成熟，药物在体内停留的时间更长。
