Seitz H K, Busenkell R, Simanowski U A, Boesche J, Kommerell B, Rojkind M
Z Gastroenterol. 1987 May;25(5):270-3.
Since colchicine has been used in the treatment of alcoholic cirrhosis of the liver, the effect of this drug on ethanol metabolism in the rat has been investigated. The acute intraperitoneal injection of colchicine (500 micrograms per kg body weight) did not significantly influence in vivo ethanol elimination rate nor the ethanol peak blood concentrations following an acute dose of ethanol (3 g per kg body weight). Cytoplasmic hepatic alcohol dehydrogenase activity was not changed by in vitro colchicine. However, an approximate 30% inhibition of hepatic microsomal ethanol oxidation was observed by colchicine at a concentration of 4 microM and more. In addition, when colchicine was given chronically in a daily dose of 50 micrograms per kg body weight for 3 weeks, again in vivo ethanol disappearance from the blood was not affected by the drug. These data indicate that neither acute nor chronic colchicine administration alters in vivo ethanol elimination. But the question is raised whether colchicine can decrease hepatic acetaldehyde concentration following a therapeutic dose in vivo by inhibiting the hepatic ethanol metabolizing enzyme system. This could be a possible explanation for the observation that alcoholics improve their liver function under colchicine therapy although they continue to drink.
由于秋水仙碱已被用于治疗酒精性肝硬化,因此对该药物对大鼠乙醇代谢的影响进行了研究。急性腹腔注射秋水仙碱(每千克体重500微克)对体内乙醇消除率以及急性给予乙醇(每千克体重3克)后的乙醇血药峰浓度均无显著影响。体外秋水仙碱未改变肝细胞质乙醇脱氢酶活性。然而,当秋水仙碱浓度为4微摩尔及更高时,观察到肝微粒体乙醇氧化受到约30%的抑制。此外,当以每千克体重50微克的日剂量长期给予秋水仙碱3周时,药物同样未影响血液中乙醇的体内消失情况。这些数据表明,急性或慢性给予秋水仙碱均不会改变体内乙醇的消除。但问题在于,秋水仙碱是否能通过抑制肝脏乙醇代谢酶系统来降低体内治疗剂量后的肝脏乙醛浓度。这可能是尽管酗酒者继续饮酒,但在秋水仙碱治疗下肝功能仍有所改善这一观察结果的一种可能解释。