Physicochemical properties, pharmacokinetics, and biodistribution of gadoteridol injection in rats and dogs.
OBJECTIVE
The physicochemical properties of gadoteridol, a macrocyclic nonionic gadolinium complex, were studied together with its pharmacokinetics and biodistribution in rats and dogs.


METHODS
Studies in rats were conducted after single intravenous injections at 0.1 or 0.35 mmol/kg using 153Gd-labeled gadoteridol or with seven daily doses of 0.1 mmol/kg to examine the levels of residual gadolinium in organs. Nonradioactive biodistribution and excretion studies were performed in dogs following injection at 0.1 mmol/kg.


RESULTS
After injection, the dose was rapidly cleared from rat blood and excreted such that more than 90% of the dose appeared in the urine within 4 hr of injection. At 7 and 14 days postinjection, only extremely low levels of gadolinium were observed in liver and bone; these levels were two to eight times lower than the levels reported after the injection of gadopentetate dimeglumine.


CONCLUSIONS
The extracellular distribution and rapid urinary excretion of gadoteridol is in agreement with data obtained with other gadolinium-containing chelates used as intravascular magnetic resonance imaging contrast agents. Differences observed in the long-term retention of gadolinium between gadoteridol and gadopentetate dimeglumine were consistent with the reported greater in vivo resistance to transmetallation of gadolinium macrocycles compared with the linear gadolinium chelate molecules.
Eakins
M N
MN
Bracco Research USA, New Brunswick, NJ 08903-0191, USA.
Eaton
S M
SM
Fisco
R A
RA
Hunt
R J
RJ
Ita
C E
CE
Katona
T
T
Owies
L M
LM
Schramm
E
E
Sulner
J W
JW
Thompson
C W
CW
D000818:Animals; D001345:Autoradiography; D001842:Bone and Bones / Q000378:metabolism; D003287:Contrast Media / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D004285:Dogs / Q000378:metabolism*; D005260:Female; D005682:Gadolinium / Q000493:pharmacokinetics; D006571:Heterocyclic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007275:Injections, Intravenous; D008099:Liver / Q000378:metabolism; D008297:Male; D009942:Organometallic Compounds / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D009994:Osmolar Concentration; D011868:Radioisotopes; D051381:Rats; D017207:Rats, Sprague-Dawley / Q000378:metabolism*; D014018:Tissue Distribution; D014783:Viscosity
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D011868:Radioisotopes; C062402:gadoteridol; D005682:Gadolinium