Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates.
The pharmacokinetics of [123I]iomazenil (Ro 16-0154) in 5 healthy human volunteers were compared to those in 2 hypothermic and 3 normothermic anesthetized monkeys. Following intravenous injection in humans and monkeys, [123I]iomazenil rapidly diffused outside the vascular bed and was cleared from the arterial plasma triexponentially. The clearance half-times in hypothermic animals were protracted to values closer to those of the human. [123I]Iomazenil was metabolized mainly to a polar radiometabolite (not extracted by ethyl acetate) in the human whereas an additional lipophilic radiometabolite was detected in the monkey. In vitro and in vivo studies showed that [123I]iomazenil established equal concentrations in association with the cellular and plasma component of the blood, indicating that the plasma clearance of [123I]iomazenil mirrors that of the blood. Analysis of organs from a monkey given [123I]iomazenil showed that the parent compound was actively taken up by peripheral organs; the polar radiometabolite accumulated mainly in the bile and the kidneys whereas the non-polar radiometabolite accumulated in the urine and kidneys. Greater than 90% of the radioactivity in the different regions of the brain was unchanged parent [123I]iomazenil.
Zoghbi
S S
SS
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06510.
Baldwin
R M
RM
Seibyl
J P
JP
al-Tikriti
M S
MS
Zea-Ponce
Y
Y
Laruelle
M
M
Sybirska
E H
EH
Woods
S W
SW
Goddard
A W
AW
Malison
R T
RT
D000328:Adult; D000818:Animals; D005260:Female; D005442:Flumazenil / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D006801:Humans; D007457:Iodine Radioisotopes; D008297:Male; D010215:Papio; D011485:Protein Binding; D011963:Receptors, GABA-A / Q000032:analysis*; D014018:Tissue Distribution; D015899:Tomography, Emission-Computed, Single-Photon
D007457:Iodine Radioisotopes; D011963:Receptors, GABA-A; D005442:Flumazenil; C063038:iomazenil