McClain D A, Hug C C
Clin Pharmacol Ther. 1980 Jul;28(1):106-14. doi: 10.1038/clpt.1980.138.
Fentanyl is considered to be a short-acting narcotic analgesic but prolonged and recurrent ventilatory depression has been reported. We examined fentanyl kinetics and excretion in 7 healthy male subjects who were given a 3.2- or 6.4-micrograms/kg dose of 3H-fentanyl intravenously. Arterial blood and urine samples were analyzed for unchanged fentanyl and total radioactivity. Fentanyl concentrations fell rapidly and 98.6% of the dose was eliminated from plasma in 60 min but the terminal elimination phase of fentanyl from the body was slow (t1/2 beta = 219 min) due to the slow return of the unchanged drug from a peripheral compartment to the central compartment where elimination occurred primarily by biotransformation. Eighty-five percent of the dose was recovered in urine and feces in 72 hr; less than 8% was recovered as unchanged fentanyl. There were fluctuations in plasma fentanyl levels during the elimination phase in all cases. The long t1/2 beta and fluctuations in plasma levels may contribute to prolonged and recurrent ventilatory effects of fentanyl.
芬太尼被认为是一种短效麻醉性镇痛药，但已有报道称其会导致长时间和反复的呼吸抑制。我们对7名健康男性受试者进行了研究，他们静脉注射了3.2或6.4微克/千克剂量的³H-芬太尼，我们检测了芬太尼的动力学和排泄情况。对动脉血和尿液样本进行分析，以检测未变化的芬太尼和总放射性。芬太尼浓度迅速下降，60分钟内98.6%的剂量从血浆中消除，但芬太尼从体内的终末消除阶段较慢（t1/2β = 219分钟），这是因为未变化的药物从外周室缓慢返回中央室，而在中央室主要通过生物转化进行消除。72小时内85%的剂量在尿液和粪便中回收；回收的未变化芬太尼不到8%。在所有情况下，消除阶段血浆芬太尼水平都有波动。较长的t1/2β和血浆水平波动可能导致芬太尼产生长时间和反复的呼吸效应。
