Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates

Sami S. Zoghbi, Ronald M. Baldwin, John P. Seibyl, Mohammed S. Al-Tikriti, Yolanda Zea-Ponce, Marc Laruelle, Elzbieta H. Sybirska, Scott W. Woods, Andrew W. Goddard, Robert T. Malison, Ralf Zimmerman, Dennis S. Charney, Eileen O. Smith, Paul B. Hoffer, Robert B. Innis

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Abstract

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]lomazenil 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.

Original languageEnglish (US)
Pages (from-to)881-888
Number of pages8
JournalInternational Journal of Radiation Applications and Instrumentation.
Volume19
Issue number8
DOIs
StatePublished - Nov 1992

ASJC Scopus subject areas

  • Medicine(all)

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    Zoghbi, S. S., Baldwin, R. M., Seibyl, J. P., Al-Tikriti, M. S., Zea-Ponce, Y., Laruelle, M., Sybirska, E. H., Woods, S. W., Goddard, A. W., Malison, R. T., Zimmerman, R., Charney, D. S., Smith, E. O., Hoffer, P. B., & Innis, R. B. (1992). Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates. International Journal of Radiation Applications and Instrumentation., 19(8), 881-888. https://doi.org/10.1016/0883-2897(92)90174-W