[Pharmacokinetics of 123I-iomazenil, a benzodiazepine receptor seeker].
The biodistribution, metabolism and excretion of 123I-iomazenil have been studied in rats, rabbits and humans following i.v. administration. In all the species, 123I-iomazenil was rapidly metabolized and more than 90% of the administrated radioactivity was excreted within the first 24 hr. Dominant metabolites were acid metabolite (R-COOH), glucuronide of the acid (R-COOH-Glc) and free iodide (I-) in rats and humans. On the other hand, R-COOH, oxidative metabolite (R'-CH2COOH) and I- were found in rabbits. Thus, the possible metabolic pathways of iomazenil were hydrolysis, oxidation, conjugation and deiodination. The radioactivity was excreted into both urine and feces in rats, while primary route of excretion in rabbits and humans was from the kidneys. At 3 hr after injection, more than 97% of the radioactivity in rat brain was found in the form of the parent compound. This result indicates that metabolites of 123I-iomazenil do not cross the blood-brain barrier.
Central Research Laboratory, Nihon Medi-Physics Co., Ltd., Chiba.
H
H
Yoshimura
A
A
Yanai
H
H
Matsumoto
K
K
Ida
M
M
Kurami
Y
Y
Yonekura
K
K
Torizuka
D000818:Animals; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes / Q000378:metabolism / Q000493:pharmacokinetics*; D008297:Male; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000187:drug effects*; D014018:Tissue Distribution
D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil