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
Department of Diagnostic Radiology, Yale University School of Medicine, New Haven, CT 06510.
Int J Rad Appl Instrum B. 1992 Nov;19(8):881-8. doi: 10.1016/0883-2897(92)90174-w.
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.
将5名健康人类志愿者体内的[123I]艾美拉唑（Ro 16 - 0154）药代动力学与2只体温过低和3只体温正常的麻醉猴进行了比较。在人类和猴体内静脉注射后，[123I]艾美拉唑迅速扩散到血管床外，并以三指数形式从动脉血浆中清除。体温过低动物的清除半衰期延长至更接近人类的数值。在人类中，[123I]艾美拉唑主要代谢为一种极性放射性代谢物（不被乙酸乙酯萃取），而在猴体内检测到另外一种亲脂性放射性代谢物。体外和体内研究表明，[123I]艾美拉唑在血液的细胞和血浆成分中建立了相等的浓度，这表明[123I]艾美拉唑的血浆清除率反映了血液的清除率。对一只给予[123I]艾美拉唑的猴的器官分析表明，母体化合物被外周器官主动摄取；极性放射性代谢物主要积聚在胆汁和肾脏中，而非极性放射性代谢物积聚在尿液和肾脏中。大脑不同区域中超过90%的放射性是未变化的母体[123I]艾美拉唑。
