[Muscular irritation study of gadobenate dimeglumine formulation (E7155) in rabbits].
To examine the local muscular irritation potency of gadobenate dimeglumine formulation (E7155), E7155 was injected into the right vastus lateralis muscle of male Kbl:JW rabbits, and saline as the negative control was injected into the left muscle. Half of the animals were subjected to necropsy at 2 or 14 days after administration. The muscles were examined macroscopically and histopathologically. Also, 0.425 w/v% and 1.7 w/v% acetic acid solutions were used as a positive control. In macroscopic observation, hemorrhage with white or brown coloration was seen in the muscles treated with E7155 at 2 days after administration, and white coloration was seen in one case at 14 days after administration. In histopathological examination, slight or moderate hemorrhage, edema, cellular infiltration, degeneration of muscle fibers and necrosis of muscle fibers were seen in the muscles treated with E7155 at 2 days after administration, and very slight to slight cellular infiltration, degeneration of muscle fibers, fibrosis, calcification of muscle fibers and foreign body giant cells were seen in the muscles treated with E7155 at 14 days after administration. The changes in the muscle caused by E7155 were definitely less than those caused by the 1.7 w/v% acetic acid solution at both 2 and 14 days, and slightly less and definitely less than those caused by the 0.425 w/v% acetic acid solution at 2 days and 14 days after administration, respectively. The changes caused by E7155 were more severe than those caused by saline. It was concluded that the local muscular irritation potency of E7155 could be classified at Grade 2.
Mikami
T
T
Department of Developmental Safety Assessment Research, Eisai Co., Ltd., Gifu, Japan.
Sagami
F
F
Tirone
P
P
Morisetti
A
A
Bussi
S
S
Yamada
Y
Y
Kimura
H
H
Goto
K
K
D000818:Animals; D003287:Contrast Media / Q000633:toxicity*; D005682:Gadolinium / Q000633:toxicity*; D007273:Injections, Intramuscular / Q000009:adverse effects; D007509:Irritants; D008279:Magnetic Resonance Imaging; D008297:Male; D008536:Meglumine / Q000031:analogs & derivatives* / Q000633:toxicity; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000473:pathology; D009336:Necrosis; D009942:Organometallic Compounds / Q000633:toxicity*; D011817:Rabbits
D003287:Contrast Media; D007509:Irritants; D009942:Organometallic Compounds; C064572:gadobenic acid; D008536:Meglumine; D005682:Gadolinium