滥用吸入剂 1,1-二氟乙烷在大鼠体内的摄取和分布。
Uptake and distribution of the abused inhalant 1,1-difluoroethane in the rat.
机构信息
Department of Pharmaceutical Sciences, St. John's University, Jamaica, New York 11554, USA.
出版信息
J Anal Toxicol. 2010 Sep;34(7):381-8. doi: 10.1093/jat/34.7.381.
1,1-Difluoroethane (DFE) is a halogenated hydrocarbon used as a propellant in products designed for dusting electronic equipment and air brush painting. When abused, inhaled DFE produces intoxication and loss of muscular coordination. To investigate DFE toxicokinetics, groups (n = 3) of Sprague-Dawley rats were exposed to 30 s of 20 L/min DFE. The experimental model was designed to mimic exposure during abuse, a protocol which has not been conducted. Tissue collection (blood, brain, heart, liver, and kidney) occurred at 0, 10, 20, 30, 45, 60, 120, 240, 480, and 900 s. Average peak DFE levels were blood 352, brain 519, heart 338, liver 187, and kidney 364 mg/L or mg/kg. The total percent uptake of the administered dose was 4.0%. Uptake into individual compartments was 2.72, 0.38, 0.15, 0.41, and 0.32% for blood, brain, heart, liver, and kidney, respectively. All animals showed signs of intoxication within 20 s manifested as lethargy, prostration and loss of righting reflex. Marked intoxication continued for about 4 min when DFE averaged 21 mg/L in blood and 17 mg/kg in brain. Between 4 and 8 min, animals continued to show signs of sedation as evidenced by reduced aggression and excitement during handling. No discernable intoxication was evident after 8 min and blood and brain levels had fallen to 10 and 6 mg/L or kg, respectively. Plots of concentration (log) versus time were consistent with a two compartment model. Initial distribution was rapid with average half life (t((1/2))) during the alpha phase of 9 s for blood, 18 s for brain and 27 s in cardiac tissue. During beta slope elimination average t((1/2)) was 86 s in blood, 110 s in brain and 168 s in heart. Late elimination half lives were longer with blood gamma = 240 s, brain gamma = 340 s, and heart gamma = 231 s. Following acute exposure the Vd = 0.06 L, beta = 0.48 min(-1), AUC = 409.8 mg.min L(-1), and CL from blood was 0.03 L min(-1). The calculated toxicokinetic data may underestimate these parameters if DFE is abused chronically due to continued uptake into lowly perfused tissues with repeated dosing.
1,1-二氟乙烷（DFE）是一种卤代烃，用作设计用于除尘电子设备和空气画笔绘画的产品中的推进剂。滥用时，吸入的 DFE 会导致中毒和肌肉协调能力丧失。为了研究 DFE 的毒代动力学，将（n = 3）组 Sprague-Dawley 大鼠暴露于 20 L/min 的 DFE 30 秒。实验模型旨在模拟滥用期间的暴露，这是一种尚未进行的方案。在 0、10、20、30、45、60、120、240、480 和 900 s 时采集血液、大脑、心脏、肝脏和肾脏等组织。平均峰值 DFE 水平为血液 352、大脑 519、心脏 338、肝脏 187 和肾脏 364 mg/L 或 mg/kg。给予剂量的总吸收率为 4.0%。进入各个隔室的摄取量分别为血液 2.72%、大脑 0.38%、心脏 0.15%、肝脏 0.41%和肾脏 0.32%。所有动物在 20 秒内出现中毒迹象，表现为嗜睡、虚弱和失去翻正反射。当血液中的 DFE 平均为 21 mg/L，大脑中的 DFE 平均为 17 mg/kg 时，中毒症状持续约 4 分钟。在 4 到 8 分钟之间，动物继续表现出镇静迹象，这表明在处理过程中攻击性和兴奋度降低。8 分钟后，没有明显的中毒迹象，血液和大脑中的 DFE 水平分别下降到 10 和 6 mg/L 或 kg。浓度（对数）与时间的关系图与双隔室模型一致。初始分布迅速，平均半衰期（t((1/2)))在 alpha 相期间为 9 s（血液）、18 s（大脑）和 27 s（心脏组织）。在 beta 斜率消除过程中，平均 t((1/2))在血液中为 86 s，在大脑中为 110 s，在心脏中为 168 s。后期消除半衰期较长，血液 gamma = 240 s，大脑 gamma = 340 s，心脏 gamma = 231 s。急性暴露后，Vd = 0.06 L，β = 0.48 min(-1)，AUC = 409.8 mg.min L(-1)，从血液中清除 CL 为 0.03 L min(-1)。如果 DFE 由于持续摄入低灌注组织和重复给药而被慢性滥用，计算出的毒代动力学数据可能会低估这些参数。
Zotero 插件