TISSUE REDISTRIBUTION OF FENTANYL AND TERMINATION OF ITS EFFECTS IN RATS
TISSUE REDISTRIBUTION OF FENTANYL AND TERMINATION OF ITS EFFECTS IN RATS
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DOI：
10.1097/00000542-198110000-00006
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发表时间：
1981-01-01
期刊：
影响因子：
8.8
通讯作者：
MURPHY, MR
中科院分区：
文献类型：
--
作者：
HUG, CC;MURPHY, MR
芬太尼从血浆中消除的动力学表明其快速和广泛的组织吸收。测定芬太尼血药浓度与组织浓度的关系。静脉注射3 H-柠檬酸芬太尼（50 μ g/kg）的6只大鼠在以下时间的每一个处死：注射后1.5、5、15、30、60、120和240分钟。分析组织中的原型3 H-枸橼酸芬太尼和总3 H-放射性。芬太尼效应在注射后10秒明显;恢复在5分钟开始，并在60分钟内完成。脑、心脏和肺中的芬太尼浓度在1.5分钟前与血浆中的芬太尼浓度平衡，并以相同的速率下降（t1/2 α）。= 8 min，t1/2 β= 45分钟）。肌肉和脂肪的芬太尼摄取较慢，与血浆平衡发生120分钟。肌肉积累了56%的剂量在5分钟内，脑芬太尼水平下降了90%。在5分钟时，只有6%的剂量在脂肪中，但在30分钟时增加到最大值17%。芬太尼被广泛代谢;代谢物在15分钟时占身体3 H放射性的25%，在4小时时占80%。芬太尼作用的持续时间短可能是由于其从大脑中的作用部位快速重新分布到储存部位（肌肉和脂肪）和生物转化部位（肝脏）。芬太尼从体内的消除可能受其从储存部位的再摄取及其在肝脏中的代谢的控制。大部分剂量最终以芬太尼代谢物的形式经尿液排泄。
The kinetics of fentanyl elimination from plasma suggest its rapid and extensive uptake by tissues. The relationships between tissue and plasma concentration of fentanyl were determined. Six rats injected i.v. with 3H-fentanyl citrate (50 .mu.g/kg) were sacrificed at each of the following times: 1.5, 5, 15, 30, 60, 120 and 240 min after injection. Tissues were analyzed for unchanged 3H-fentanyl citrate and for total 3H-radioactivity. Fentanyl effects were evident 10 s after injection; recovery began at 5 min and was complete within 60 min. Fentanyl concentrations in brain, heart and lung equilibrated with that in plasma before 1.5 min and declined at the same rate (t1/2.alpha. = 8 min, t1/2.beta. = 45 min). Fentanyl uptake by muscle and fat was slower and equilibration with plasma occurred by 120 min. Muscle accumulated 56% of the dose within 5 min, by which time brain fentanyl levels had declined by 90%. Only 6% of the dose was in fat at 5 min but this increased to a maximum of 17% at 30 min. Fentanyl was extensively metabolized; metabolites represented 25% of body 3H-radioactivity at 15 min and 80% at 4 h. The short duration of fentanyl effect is probably due to its rapid redistribution from sites of action in the brain to sites of storage (muscle and fat) and biotransformation (liver). The elimination of fentanyl from the body may be governed by its reuptake from storage sites and its metabolism in the liver. Most of the dose is ultimately excreted in the form of fentanyl metabolites in urine.