Breimer L T, Hennis P J, Burm A G, Danhof M, Bovill J G, Spierdijk J, Vletter A A
Department of Anaesthesiology, University Hospital, Leiden, The Netherlands.
Clin Pharmacokinet. 1991 Jun;20(6):491-6. doi: 10.2165/00003088-199120060-00005.
The effect of intravenous flumazenil 10 mg on the electroencephalogram (EEG) was investigated in 7 volunteers in a placebo-controlled, randomised, double-blind, crossover study. The EEG was recorded between Fp1-M1 and Fp2-M2 and analysed using an aperiodic analysis technique. Two volunteers were excluded from the study because of significant asymmetry between baseline EEG recordings of the left and right hemisphere, in the remainder there were no changes in the beta-frequency range (12 to 30 Hz) or in other ranges of the EEG during or after flumazenil or placebo administration, with regard to the parameters total number of waves per second or total amplitude per second. There were no changes in heart rate, respiratory rate or blood pressure after administration of flumazenil or placebo. Three volunteers reported feelings of 'pressure to move' during the initial 2 min of the flumazenil infusion. The pharmacokinetics of flumazenil were investigated in the same volunteers. Flumazenil 10 mg was administered intravenously over 10 min; the data from 1 volunteer were excluded from this analysis because of blood sampling problems. The plasma concentration-time data of the remaining 6 volunteers were characterised by a biexponential function. The pharmacokinetic parameters were (mean +/- SD): initial volume of distribution, 16 +/- 5.7L; volume of distribution at steady-state, 64.8 +/- 12.5L; total body clearance, 53.8 +/- 1.2 L/h; distribution half-life, 4.1 +/- 1.3 min; and elimination half-life, 70.2 +/- 9.9 min. The authors conclude that flumazenil has no significant EEG effects. The rapid distribution and elimination of flumazenil may explain its previously reported short duration of action after intravenous anaesthesia with high doses of midazolam.
在一项安慰剂对照、随机、双盲、交叉研究中，对7名志愿者研究了静脉注射10毫克氟马西尼对脑电图（EEG）的影响。EEG记录于Fp1-M1和Fp2-M2之间，并使用非周期性分析技术进行分析。两名志愿者因左右半球基线EEG记录存在明显不对称而被排除在研究之外，其余志愿者在注射氟马西尼或安慰剂期间及之后，EEG的β频率范围（12至30赫兹）或其他范围在每秒总波数或每秒总振幅参数方面没有变化。注射氟马西尼或安慰剂后，心率、呼吸频率或血压没有变化。三名志愿者在注射氟马西尼的最初2分钟内报告有“想要动的压迫感”。在相同志愿者中研究了氟马西尼的药代动力学。静脉注射10毫克氟马西尼历时10分钟；由于采血问题，1名志愿者的数据被排除在该分析之外。其余6名志愿者的血浆浓度-时间数据符合双指数函数特征。药代动力学参数为（均值±标准差）：初始分布容积，16±5.7升；稳态分布容积，64.8±12.5升；全身清除率，53.8±1.2升/小时；分布半衰期，4.1±1.3分钟；消除半衰期，70.2±9.9分钟。作者得出结论，氟马西尼对EEG没有显著影响。氟马西尼的快速分布和消除可能解释了其先前报道的在大剂量咪达唑仑静脉麻醉后作用持续时间短的现象。
