PHARMACOKINETICS OF THE SPECT BENZODIAZEPINE RECEPTOR RADIOLIGAND [I-123] IOMAZENIL IN HUMAN AND NONHUMAN-PRIMATES

The pharmacokinetics of [I-123]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, [I-123]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. [I-123]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 [I-123]iomazenil established equal concentrations in association with the cellular and plasma component of the blood, indicating that the plasma clearance of [I-123]iomazenil mirrors that of the blood. Analysis of organs from a monkey given [I-123]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 [I-123]iomazenil.