Miki S, Asanuma Y, Une M, Hoshita T
Department of Surgery I, Kyushu University School of Medicine, Fukuoka, Japan.
J Pharmacobiodyn. 1990 Oct;13(10):637-46. doi: 10.1248/bpb1978.13.637.
Intestinal absorption and metabolism of 3,7-dioxo-5 beta-cholanoic acid, were studied in the bile fistula rats, hamsters, guinea-pigs and rabbits. The influence of dose (1 and 100 mg/kg) on the absorption and the metabolism was also estimated. The dioxo bile acid was absorbed efficiently from the intestine and quickly excreted into bile in these animals. Large dose did not retard the absorption rate and showed a significant choleretic effect for a few hours. Species differences were observed in the metabolism of this compound. In hamsters and guinea-pigs, most of the metabolites in the bile were conjugated with either taurine or glycine. The proportion of bile acids amidated with glycine was greater with the large dose. In rats, the biliary metabolites were conjugated with taurine, but not with glycine, whereas in rabbits, glycine conjugates were the only recovered metabolites. Unconjugated metabolites were also detected in the bile of the rodents, and the proportion of them rose to 17-29% after the administration of 100 mg/kg quantities. A small part of unchanged 3,7-dioxo-5 beta-cholanoic acid was excreted into the bile as both the conjugated and unconjugated forms in these animals. The greater part of this compound administered was metabolized to 7-ketolithocholic acid, chenodeoxycholic acid and ursodeoxycholic acid. In hamsters and guinea-pigs, chenodeoxycholic acid was a greater metabolite of this compound than ursodeoxycholic acid, while in rats and rabbits, the amount of ursodeoxycholic acid exceeded that of chenodeoxycholic acid. In rats, the resulting dihydroxy bile acids were further metabolized to alpha- and beta-muricholic acids.
在胆瘘大鼠、仓鼠、豚鼠和兔子中研究了3,7-二氧代-5β-胆烷酸的肠道吸收和代谢。还评估了剂量(1和100mg/kg)对吸收和代谢的影响。在这些动物中,二氧代胆汁酸从肠道有效吸收并迅速排泄到胆汁中。大剂量并未延缓吸收率,并且在数小时内显示出显著的利胆作用。观察到该化合物代谢存在种属差异。在仓鼠和豚鼠中,胆汁中的大多数代谢物与牛磺酸或甘氨酸结合。大剂量时与甘氨酸酰胺化的胆汁酸比例更高。在大鼠中,胆汁代谢物与牛磺酸结合,但不与甘氨酸结合,而在兔子中,甘氨酸结合物是唯一回收的代谢物。在啮齿动物的胆汁中也检测到未结合的代谢物,给予100mg/kg剂量后,它们的比例升至17-29%。在这些动物中,一小部分未改变的3,7-二氧代-5β-胆烷酸以结合和未结合形式排泄到胆汁中。给予的该化合物大部分代谢为7-酮石胆酸、鹅去氧胆酸和熊去氧胆酸。在仓鼠和豚鼠中,该化合物的主要代谢产物是鹅去氧胆酸而非熊去氧胆酸,而在大鼠和兔子中,熊去氧胆酸的量超过鹅去氧胆酸。在大鼠中,生成的二羟基胆汁酸进一步代谢为α-和β-鼠胆酸。