Schleimer R, Benjamini E, Eisele J, Henderson G
Clin Pharmacol Ther. 1978 Feb;23(2):188-94. doi: 10.1002/cpt1978232188.
The pharmacokinetics of fentanyl were determined in human surgical patients using radioimmunoassay. Fentanyl was measured in the serum, cerebrospinal fluid (CSF), and urine of patients receiving 0.1, 0.5, or 1.0 mg/m2 of fentanyl intravenously. The kinetics of the disappearance of fentanyl from the serum were very similar at the three administered doses. At all doses, levels fell rapidly in the first five minutes to approximately 20% of the peak value. Thereafter, serum levels fell more slowly with an observed half-life (t 1/2) of approximately 10 to 20 min. depending on dose. By 2 hr serum levels had stabilized at low values (1, 5, and 8 ng/ml) and continued to decrease very slowly thereafter, with an observed t 1/2 of 1 to 2 hr at the low dose (0.1 mg/m2) and greater than 4 hr at 0.5 and 1.0 mg/m2. The serum elimination curves were dissected and described mathematically in terms of a three-compartment model. Urinary excretion of fentanyl accounted for 15% to 20% of the administered dose. Urinary excretion was very low during the first 2 hr, suggesting that this route of elimination is not important in terminating the actions of fentanyl in man. Fentanyl levels in the CSF of patients given terminating the actions of fentanyl in man. Fentanyl levels in the CSF of patients given the high dose (1 mg/m2) were low, and never exceeded 4 ng/ml. Peak levels of fentanyl in the CSF were not seen until at least 15 min after administration.
采用放射免疫分析法测定了芬太尼在接受外科手术的患者体内的药代动力学。对静脉注射0.1、0.5或1.0mg/m²芬太尼的患者的血清、脑脊液（CSF）和尿液进行了芬太尼测定。在这三种给药剂量下，芬太尼从血清中消失的动力学非常相似。在所有剂量下，血药浓度在前5分钟迅速下降至峰值的约20%。此后，血清水平下降得更慢，观察到的半衰期（t 1/2）约为10至20分钟，具体取决于剂量。到2小时时，血清水平已稳定在低值（1、5和8ng/ml），此后继续非常缓慢地下降，低剂量（0.1mg/m²）时观察到的t 1/2为1至2小时，0.5和1.0mg/m²时大于4小时。血清消除曲线根据三室模型进行剖析并进行数学描述。芬太尼的尿排泄量占给药剂量的15%至20%。在最初2小时内尿排泄量非常低，这表明该消除途径在终止芬太尼在人体内的作用方面并不重要。给予高剂量（1mg/m²）的患者脑脊液中的芬太尼水平较低，从未超过4ng/ml。脑脊液中芬太尼的峰值水平直到给药后至少15分钟才出现。
