Fate of tritiated didemnin B in mice: Excretion and tissue concentrations after an intraperitoneal dose
Fate of tritiated didemnin B in mice: Excretion and tissue concentrations after an intraperitoneal dose
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DOI：
10.1002/bdd.466
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发表时间：
2005-11-01
影响因子：
2.1
通讯作者：
Levengood, JM
中科院分区：
文献类型：
--
作者：
Beasley, VR;Bruno, SJ;Levengood, JM
Didemnin B 已在癌症患者中进行了试验，具有抗病毒和免疫抑制特性。 [H-3]didemnin B以320或1280μg/kg腹膜内(i.p.)给予小鼠。收集尿液和粪便直至168小时，此时处死小鼠并收集组织。另外，[H-3]didemnin B 经腹膜内给予。 320μg/kg，给药后1-120小时处死小鼠。血液中的放射性标记迅速增加，然后迅速下降。尿液、粪便和组织中的大多数放射性标记代表母体化合物。 [H-3]didemnin B 的浓度在肝脏 > 胆囊 > 与胰腺一致的下消化道 > 脾 > 与尿液一致的脂肪组织与膀胱一致的肾脏中最高。胰腺的组织终末半衰期最长，放射性最高，为 7 天。中间浓度为十二指肠、空肠>肺>髂腰肌>胃、睾丸、皮肤>心脏。低浓度位于肱骨、股骨、股四头肌、三头肌>大脑。粪便排泄占剂量的45.9%-58.3%，24小时后下降，随后增加，表明可能存在肠肝循环或昼夜节律的影响。尿排泄占剂量的18.4%-25.2%，但24小时后很少。先前发现的动物和人类敏感器官中的浓度最高。应在动物模型中评估 Didemnin B 治疗胰腺癌的效果。版权所有 (c) 2005 John Wiley & Sons, Ltd.
Didemnin B has undergone trials in cancer patients, and has antiviral and immunosuppressive properties. [H-3]didemnin B was administered intraperitoneally (i.p.) to mice at 320 or 1280 mu g/kg. Urine and feces were collected until 168 h, at which time the mice were killed and tissues collected. Additionally, [H-3]didemnin B was given i.p. at 320 mu g/kg, and mice were killed at 1-120h post-dosing. Radiolabel increased rapidly in blood then rapidly declined. Most radiolabel in urine, feces and tissues represented parent compound. Concentrations of [H-3]didemnin B were greatest in the liver > gallbladder > lower digestive tract congruent to pancreas > spleen > kidney congruent to adipose tissue congruent to urinary bladder with urine. The pancreas had the longest terminal half-life of the tissues and the highest radioactivity at 7 days. Intermediate concentrations were in the duodenum congruent to jejunum > lung > iliopsoas > stomach congruent to testes congruent to skin > heart. Low concentrations were in the humerus congruent to femur congruent to quadriceps congruent to triceps > brain. Fecal excretion accounted for 45.9%-58.3% of the dose and declined after 24 h, followed by an increase, suggesting possible enterohepatic recycling or an impact of circadian rhythms. Urinary excretion accounted for 18.4%-25.2% of the dose, but was minimal after 24 h. The concentrations were highest in organs previously found to be sensitive in animals and humans. Didemnin B should be evaluated in animal models for treatment of pancreatic cancer. Copyright (c) 2005 John Wiley & Sons, Ltd.