C. Dehaen et al., HEPATIC TRANSPORT OF THE MAGNETIC-RESONANCE-IMAGING CONTRAST AGENT GADOBENATE DIMEGLUMINE IN THE RAT, Academic radiology, 2(3), 1995, pp. 232-238
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.