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 - 1992
Externally publishedYes

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GABA-A Receptors
Single-Photon Emission-Computed Tomography
Primates
Pharmacokinetics
Haplorhini
Kidney
iomazenil
Bile
Intravenous Injections
Radioactivity
Blood Vessels
Healthy Volunteers
Urine
Brain

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Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates. / Zoghbi, Sami S.; Baldwin, Ronald M.; Seibyl, John P.; Al-Tikriti, Mohammed S.; Zea-Ponce, Yolanda; Laruelle, Marc; Sybirska, Elzbieta H.; Woods, Scott W.; Goddard, Andrew W.; Malison, Robert T.; Zimmerman, Ralf; Charney, Dennis S.; Smith, Eileen O.; Hoffer, Paul B.; Innis, Robert B.

In: International Journal of Radiation Applications and Instrumentation., Vol. 19, No. 8, 1992, p. 881-888.

Research output: Contribution to journalArticle

Zoghbi, SS, Baldwin, RM, Seibyl, JP, Al-Tikriti, MS, Zea-Ponce, Y, Laruelle, M, Sybirska, EH, Woods, SW, Goddard, AW, Malison, RT, Zimmerman, R, Charney, DS, Smith, EO, Hoffer, PB & Innis, RB 1992, 'Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates', International Journal of Radiation Applications and Instrumentation., vol. 19, no. 8, pp. 881-888. https://doi.org/10.1016/0883-2897(92)90174-W
Zoghbi, Sami S. ; Baldwin, Ronald M. ; Seibyl, John P. ; Al-Tikriti, Mohammed S. ; Zea-Ponce, Yolanda ; Laruelle, Marc ; Sybirska, Elzbieta H. ; Woods, Scott W. ; Goddard, Andrew W. ; Malison, Robert T. ; Zimmerman, Ralf ; Charney, Dennis S. ; Smith, Eileen O. ; Hoffer, Paul B. ; Innis, Robert B. / Pharmacokinetics of the SPECT benzodiazepine receptor radioligand [123I]iomazenil in human and non-human primates. In: International Journal of Radiation Applications and Instrumentation. 1992 ; Vol. 19, No. 8. pp. 881-888.
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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.",
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AU - Zoghbi, Sami S.

AU - Baldwin, Ronald M.

AU - Seibyl, John P.

AU - Al-Tikriti, Mohammed S.

AU - Zea-Ponce, Yolanda

AU - Laruelle, Marc

AU - Sybirska, Elzbieta H.

AU - Woods, Scott W.

AU - Goddard, Andrew W.

AU - Malison, Robert T.

AU - Zimmerman, Ralf

AU - Charney, Dennis S.

AU - Smith, Eileen O.

AU - Hoffer, Paul B.

AU - Innis, Robert B.

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