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全身性镧通过大鼠胆汁排出。

Systemic lanthanum is excreted in the bile of rats.

作者信息

Damment Stephen J P, Pennick Michael

机构信息

Shire Pharmaceuticals, Basingstoke, UK.

出版信息

Toxicol Lett. 2007 Jun 15;171(1-2):69-77. doi: 10.1016/j.toxlet.2007.04.005. Epub 2007 Apr 24.

Abstract

Lanthanum carbonate is a non-calcium-based oral phosphate binder for the control of hyperphosphataemia in patients with chronic kidney disease Stage 5. As part of its pre-clinical safety evaluation, studies were conducted in rats to determine the extent of absorption and routes of excretion. Following oral gavage of a single 1500 mg/kg dose, the peak plasma lanthanum concentration was 1.04+/-0.31 ng/mL, 8 h post-dose. Lanthanum was almost completely bound to plasma proteins (>99.7%). Within 24h of administration of a single oral dose, 97.8+/-2.84% of the lanthanum was recovered in the faeces of rats. Comparing plasma exposure after oral and intravenous administration of lanthanum yielded an absolute oral bioavailability of 0.0007%. Following intravenous administration of lanthanum chloride (0.3 mg/kg), 74.1+/-5.82% of the dose (96.9+/-0.50% of recovered lanthanum) was excreted in faeces in 42 days, and in bile-duct cannulated rats, 10.0+/-2.46% of the dose (85.6+/-2.97% of recovered lanthanum) was excreted in bile in 5 days. Renal excretion was negligible, with <2% of the intravenous dose recovered in urine. These studies demonstrate that lanthanum undergoes extremely low intestinal absorption and that absorbed drug is predominantly excreted in the bile.

摘要

碳酸镧是一种非钙类口服磷结合剂,用于控制慢性肾脏病5期患者的高磷血症。作为其临床前安全性评估的一部分,在大鼠中进行了研究,以确定吸收程度和排泄途径。经口单次灌胃给予1500mg/kg剂量后,给药后8小时血浆镧浓度峰值为1.04±0.31ng/mL。镧几乎完全与血浆蛋白结合(>99.7%)。单次口服给药后24小时内,97.8±2.84%的镧在大鼠粪便中回收。比较口服和静脉注射镧后的血浆暴露情况,得出绝对口服生物利用度为0.0007%。静脉注射氯化镧(0.3mg/kg)后,74.1±5.82%的剂量(回收镧的96.9±0.50%)在42天内随粪便排出,在胆管插管大鼠中,10.0±2.46%的剂量(回收镧的85.6±2.97%)在5天内随胆汁排出。肾排泄可忽略不计,静脉注射剂量中<2%在尿液中回收。这些研究表明,镧的肠道吸收极低,吸收的药物主要通过胆汁排泄。

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