Hepatic transport of the magnetic resonance imaging contrast agent gadobenate dimeglumine in the rat.
OBJECTIVE
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.


METHODS
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.


RESULTS
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%.


CONCLUSIONS
The transport of gadobenate ion from plasma to bile occurs in the rat mainly through the BSP/bilirubin transport systems.
de Haën
C
C
Research and Development Division, Magnetic Resonance, Bracco S.p.A., Milan, Italy.
Lorusso
V
V
Luzzani
F
F
Tirone
P
P
D000704:Analysis of Variance; D000818:Animals; D001663:Bilirubin / Q000097:blood; D001692:Biological Transport; D003287:Contrast Media / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine; D001663:Bilirubin