Foster B C, Gallicano K D, Whitehouse L W, McGilveray I J, Khan S R
Bureau of Drug Research, Ottawa, Ontario, Canada.
Biopharm Drug Dispos. 1990 Oct;11(7):595-606. doi: 10.1002/bdd.2510110705.
Comparative studies of oral and intravenous administration of tritiated dextran sulfate in rats showed markedly different distribution patterns. Following IV dosing about 50 per cent of the radioactivity was recovered in feces and urine within 24 h. The major portion of the recoverable dose was eliminated in the urine as dextran sulfate within 3 h after administration. In orally treated rats only about 32 per cent of the 3H was recovered in the feces and urine, the major fraction being associated with unabsorbed dextran sulfate in the feces. The remainder of the dose in both treatment groups has apparently distributed throughout the rat body with some accumulation in the liver, kidney and spleen. Consequently, the disposition of about 67 per cent or the oral dose could not be fully accounted for by these excretion routes. However, separation with Sephadex columns showed similarities in the 24 h plasma and urine profiles of the IV and orally dosed rats which suggest that while the oral dose was absorbed as dextran sulfate, it underwent rapid metabolism to small molecular weight products prior to entering the systemic circulation which were then widely distributed within the rat.
对大鼠口服和静脉注射氚标记硫酸葡聚糖的比较研究显示，其分布模式明显不同。静脉给药后，约50%的放射性在24小时内从粪便和尿液中回收。给药后3小时内，可回收剂量的大部分以硫酸葡聚糖形式经尿液排出。在口服给药的大鼠中，粪便和尿液中仅回收了约32%的3H，大部分与粪便中未吸收的硫酸葡聚糖相关。两个治疗组中其余剂量显然已分布于大鼠全身，在肝脏、肾脏和脾脏中有一定蓄积。因此，这些排泄途径无法完全解释约67%的口服剂量的处置情况。然而，用葡聚糖凝胶柱分离显示，静脉给药和口服给药大鼠在24小时血浆和尿液谱图上有相似之处，这表明虽然口服剂量以硫酸葡聚糖形式被吸收，但在进入体循环之前迅速代谢为小分子产物，然后在大鼠体内广泛分布。
