Pharmacokinetic analysis of benzodiazepine receptor binding of [123I]iomazenil in human brain.
OBJECTIVE
The purpose of this study is to evaluate the central benzodiazepine (BZP) receptor binding of iomazenil (IMZ) by pharmacokinetic analysis and to establish a methodology for the diagnosis of CNS disorders with abnormalities in BZP receptor binding.


METHODS
BZP receptor binding of IMZ was analyzed kinetically using plasma concentration-time profiles and dynamic single photon emission computed tomography (SPECT) data obtained after the intravenous administration of IMZ to patients with neuropsychiatric disease. The analysis was based on a 3-compartmental model including the processes of both blood-brain barrier (BBB) transport and BZP receptor binding.


RESULTS
Hydrolized metabolite of IMZ was detected in plasma, indicating the need for separation by HPLC. The BBB influx clearance and the receptor binding potential of IMZ in the medial temporal region was reduced in the epileptic patient.


CONCLUSIONS
Our findings suggest the possibility of detecting the epileptic focus by using our method.
Ito
K
K
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, University of Tokyo, Japan.
Momose
T
T
Kotaki
H
H
Kojima
Y
Y
Yamamoto
K
K
Katashima
M
M
Sawada
Y
Y
Sasaki
Y
Y
Iga
T
T
D001812:Blood-Brain Barrier; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D001927:Brain Diseases / Q000000981:diagnostic imaging / Q000378:metabolism*; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics; D006801:Humans; D007275:Injections, Intravenous; D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A / Q000378:metabolism*; D015899:Tomography, Emission-Computed, Single-Photon
D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil