HEPATIC TRANSPORT OF THE MAGNETIC-RESONANCE-IMAGING CONTRAST AGENT GADOBENATE DIMEGLUMINE IN THE RAT

Rationale and Objectives. Gadobenate dimeglumine is a new octadentate gadolinium (III) complex salified with meglumine. The compound is curr ently under evaluation as an intravenously administered paramagnetic c ontrast agent for magnetic resonance (MR) imaging. We investigated the mechanisms involved in the biliary excretion of gadobenate ion, the c ontrast-effective ion in gadobenate dimeglumine. Methods. Biliary and urinary excretion of gadobenate ion injected intravenously to rats at 0.25 mmol/kg was studied following pretreatment with bromosulfophthale in (BSP) disodium salt, sodium taurocholate (TC), or oxyphenonium brom ide (OF) and at various times after common bile duct ligation. Gadoben ate ion was assayed by high-pressure liquid chromatography in bile and urine. Plasma bilirubin levels after duct ligation were measured by c olorimetric assay. Results. The 90-min excretion of gadobenate ion int o 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 redu ced recovery of the compound in bile to less than 1% and increased uri nary excretion to 65.6 +/- 4.7%. Gadobenate dimeglumine had a substant ial choleretic effect that was completely abolished by pretreatment wi th BSP. Pretreatment with TC and OP did not change the biliary or urin ary 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 mu mol/L (4 days after common bile duct ligature) and d ecreased 6-hr cumulative biliary excretion of gadobenate ion from 45 /- 16% to 5.3 +/- 4.2% of the injected dose, Urinary excretion increas ed correspondingly from 49 +/- 15% to 83 +/- 12%. Conclusion. The tran sport of gadobenate ion from plasma to bile occurs in the rat mainly t hrough the BSP/bilirubin transport systems.