Brain penetration and neurological effects of gadobenate dimeglumine in the rat.
OBJECTIVE
The study aimed at measuring the amount of the gadobenate ion that crosses an experimentally disrupted blood-brain barrier (BBB) in rats following i.v. administration of gadobenate dimeglumine (GD). The intention was also to compare this amount with the minimally effective intrathecal dose that alters the cerebral function.


METHODS
Sprague Dawley rats with an osmotically disrupted BBB received 0.3 mmol/kg of (153Gd) GD, i.v. Radioactivity was measured in plasma and brain parenchyma. The effect on the cerebral function was evaluated by means of a standard motor coordination test (Rota-rod test).


RESULTS
Brain levels of the gadobenate ion were approximately 60 nmol/g tissue after i.v. injection of GD. In rats with an intact BBB, the lowest dose of GD able to slightly impair motor coordination was 0.01 mmol/kg following intracisternal injection.


CONCLUSIONS
I.v. administration of GD to rats with a disrupted BBB results in brain levels of the gadobenate ion that are more than 20 times lower than those reached following intrathecal administration of the minimal effective dose, as determined by the Rota-rod test.
Luzzani
F
F
Milan Research Centre, Bracco SpA, Milan, Italy.
Cipolla
P
P
Pélaprat
M L
ML
Robert
F
F
Gotti
C
C
Tirone
P
P
de Haën
C
C
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D003287:Contrast Media / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008297:Male; D008536:Meglumine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D003287:Contrast Media; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine