de Haën C, Lorusso V, Luzzani F, Tirone P
Research and Development Division, Magnetic Resonance, Bracco S.p.A., Milan, Italy.
Acad Radiol. 1995 Mar;2(3):232-8. doi: 10.1016/s1076-6332(05)80171-0.
Gadobenate dimeglumine is a new octadentate gadolinium (III) complex salified with meglumine. The compound is currently under evaluation as an intravenously administered paramagnetic contrast agent for magnetic resonance (MR) imaging. We investigated the mechanisms involved in the biliary excretion of gadobenate ion, the contrast-effective ion in gadobenate dimeglumine.
Biliary and urinary excretion of gadobenate ion injected intravenously to rats at 0.25 mmol/kg was studied following pretreatment with bromosulfophthalein (BSP) disodium salt, sodium taurocholate (TC), or oxyphenonium bromide (OP) and at various times after common bile duct ligation. Gadobenate ion was assayed by high-pressure liquid chromatography in bile and urine. Plasma bilirubin levels after duct ligation were measured by colorimetric assay.
The 90-min excretion of gadobenate ion into bile accounted for 35.5 +/- 3.7% and excretion into urine for 45.7 +/- 3.5% of the injected dose (mean +/- SD). Pretreatment with BSP reduced recovery of the compound in bile to less than 1% and increased urinary excretion to 65.6 +/- 4.7%. Gadobenate dimeglumine had a substantial choleretic effect that was completely abolished by pretreatment with BSP. Pretreatment with TC and OP did not change the biliary or urinary excretion of gadobenate ion. Surgical cholestasis led to a massive increase in plasma bilirubin levels from 3.9 +/- 2.2 (day of surgery) to 129 +/- 37 mumol/L (4 days after common bile duct ligature) and decreased 6-hr cumulative biliary excretion of gadobenate ion from 45 +/- 16% to 5.3 +/- 4.2% of the injected dose. Urinary excretion increased correspondingly from 49 +/- 15% to 83 +/- 12%.
The transport of gadobenate ion from plasma to bile occurs in the rat mainly through the BSP/bilirubin transport systems.
钆布醇是一种新的与葡甲胺成盐的八齿钆（III）配合物。该化合物目前正在作为一种静脉注射用顺磁性造影剂进行磁共振（MR）成像评估。我们研究了钆布醇离子（钆布醇中的造影有效离子）经胆汁排泄的相关机制。
在大鼠经溴磺酚酞（BSP）二钠盐、牛磺胆酸钠（TC）或溴化氧苯戊铵（OP）预处理后，以及在胆总管结扎后的不同时间，研究以0.25 mmol/kg静脉注射钆布醇离子后其在胆汁和尿液中的排泄情况。通过高压液相色谱法测定胆汁和尿液中的钆布醇离子。采用比色法测定结扎胆管后血浆胆红素水平。
钆布醇离子在90分钟内排入胆汁的量占注射剂量的35.5±3.7%，排入尿液的量占注射剂量的45.7±3.5%（均值±标准差）。用BSP预处理后，该化合物在胆汁中的回收率降至1%以下，而尿排泄增加至65.6±4.7%。钆布醇具有显著的利胆作用，但用BSP预处理可完全消除该作用。用TC和OP预处理并未改变钆布醇离子的胆汁或尿液排泄。手术性胆汁淤积导致血浆胆红素水平从3.9±2.2（手术日）大幅升至129±37 μmol/L（胆总管结扎后4天），并使钆布醇离子6小时的累积胆汁排泄量从注射剂量的45±16%降至5.3±4.2%。尿排泄量相应地从49±15%增至83±12%。
在大鼠中，钆布醇离子从血浆到胆汁的转运主要通过BSP/胆红素转运系统进行。
