Jones R D, Chan K, Roulson C J, Brown A G, Smith I D, Mya G H
Department of Anaesthesiology, University of Hong Kong.
Br J Anaesth. 1993 Mar;70(3):286-92. doi: 10.1093/bja/70.3.286.
We have studied simultaneously the pharmacokinetics of flumazenil and midazolam in 12 healthy Chinese children, aged 5-9 yr, undergoing circumcision. Two hours before operation each patient received midazolam 0.5 mg kg-1 orally for premedication and 0.5 mg kg-1 i.v. during induction. Six minutes after cessation of anaesthesia, a bolus of flumazenil 10 micrograms kg-1 was given i.v., followed by an infusion of flumazenil at 5 micrograms kg-1 min-1 which was maintained until the child could identify himself. Midazolam data were consistent with a three-compartment model with a mean (SD) elimination half-life of 107 (30) min, total body clearance of 15.4 (3.2) ml min-1 kg-1 and apparent volume of distribution at steady state of 1.9 (0.6) litre kg-1. Flumazenil data were best interpreted by a monoexponential function, with a mean terminal elimination half-life of 35.3 (13.8) min, a total plasma clearance of 20.6 (6.9) ml min-1 kg-1 and apparent volume of distribution at steady state of 1.0 (0.2) litre kg-1. No unchanged midazolam was detected in the 24-h urine sample, but 5.8-13.8% of the flumazenil dose was recovered unchanged. At the time of self identification, 4.5 (1.4) min after flumazenil administration, the mean plasma concentrations of midazolam and flumazenil were 163.1 (43.7) and 29.9 (16.1) ng ml-1, respectively.
我们同时研究了氟马西尼和咪达唑仑在12名5至9岁接受包皮环切术的健康中国儿童体内的药代动力学。手术前两小时，每位患者口服咪达唑仑0.5 mg/kg进行术前用药，并在诱导期间静脉注射0.5 mg/kg。麻醉停止后6分钟，静脉注射10 μg/kg的氟马西尼推注剂量，随后以5 μg/kg·min-1的速度输注氟马西尼，持续至患儿能认出自己。咪达唑仑的数据符合三室模型，平均（标准差）消除半衰期为107（30）分钟，全身清除率为15.4（3.2）ml·min-1·kg-1，稳态表观分布容积为1.9（0.6）L/kg。氟马西尼的数据最好用单指数函数解释，平均终末消除半衰期为35.3（13.8）分钟，总血浆清除率为20.6（6.9）ml·min-1·kg-1，稳态表观分布容积为1.0（0.2）L/kg。在24小时尿液样本中未检测到未代谢的咪达唑仑，但氟马西尼剂量的5.8 - 13.8%以原形回收。在氟马西尼给药后4.5（1.4）分钟患儿能认出自己时，咪达唑仑和氟马西尼的平均血浆浓度分别为163.1（43.7）和29.9（16.1）ng/ml。
