可待因代谢的种属差异：小鼠、大鼠、豚鼠和兔体内可待因葡萄糖醛酸苷、吗啡-3-葡萄糖醛酸苷和吗啡-6-葡萄糖醛酸苷的尿排泄情况

Species differences in metabolism of codeine: urinary excretion of codeine glucuronide, morphine-3-glucuronide and morphine-6-glucuronide in mice, rats, guinea pigs and rabbits.

Oguri K, Hanioka N, Yoshimura H

Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.

Xenobiotica. 1990 Jul;20(7):683-8. doi: 10.3109/00498259009046884.

Abstract

Metabolites of codeine were determined by use of h.p.l.c. in urine of male mice, rats, guinea pigs and rabbits injected with 10 mg codeine/kg subcutaneously. 2. In 24 h urines of these species, unchanged codeine, codeine glucuronide, free morphine, and morphine-3-glucuronide were as follows: mice, 6.8, 1.6, 0.8 and 7.6% dose; rats, 1.6, 0.2, 4.3 and 23.9% dose; guinea pigs, 1.6, 39.8, 0.2 and 1.6% dose; rabbits, 2.2, 24.5, 1.3 and 17.9% dose. Urinary excretion of morphine-6-glucuronide was 0.7% dose in guinea pigs, 1.9% in rabbits, and not detectable in mice and rats. Norcodeine was found only in the urine of mice. 3. These results indicate that codeine is metabolized in all four species by glucuronidation and by oxidative N- and O-demethylation, but the quantitative excretions of metabolites were quite different in different species.

摘要

通过高效液相色谱法（h.p.l.c.）测定了皮下注射10毫克/千克可待因的雄性小鼠、大鼠、豚鼠和兔子尿液中的可待因代谢物。2. 在这些物种的24小时尿液中，未变化的可待因、可待因葡萄糖醛酸苷、游离吗啡和吗啡-3-葡萄糖醛酸苷的含量如下：小鼠，分别为剂量的6.8%、1.6%、0.8%和7.6%；大鼠，分别为剂量的1.6%、0.2%、4.3%和23.9%；豚鼠，分别为剂量的1.6%、39.8%、0.2%和1.6%；兔子，分别为剂量的2.2%、24.5%、1.3%和17.9%。豚鼠尿液中吗啡-6-葡萄糖醛酸苷的排泄量为剂量的0.7%，兔子为1.9%，在小鼠和大鼠尿液中未检测到。去甲可待因仅在小鼠尿液中被发现。3. 这些结果表明，可待因在所有这四个物种中均通过葡萄糖醛酸化以及氧化N-去甲基化和O-去甲基化进行代谢，但不同物种中代谢物的定量排泄情况差异很大。