Park G R, Manara A R, Dawling S
Department of Anaesthesia, Addenbrooke's Hospital, Cambridge.
Br J Clin Pharmacol. 1989 May;27(5):634-7. doi: 10.1111/j.1365-2125.1989.tb03429.x.
Six patients received 10 mg of midazolam intravenously during the anhepatic period of liver transplantation. Arterial blood was sampled during this time and for a similar period following revascularisation. The plasma was analysed using gas chromatography and electron capture detection (GC-ECD) for midazolam alpha-hydroxymidazolam and alpha-hydroxymidazolam glucuronide. Five of the six patients had small but significant concentrations of metabolites detected during the anhepatic period, demonstrating the presence of extra-hepatic sites of metabolism for this drug. The remaining patient had plasma concentrations of metabolites below the lower limit of detection (2 micrograms l-1). This may represent a pharmacogenetic abnormality or a temporary failure of midazolam metabolism secondary to the patients illness affecting the extra-hepatic sites of metabolism.
六名患者在肝移植无肝期接受了10毫克咪达唑仑静脉注射。在此期间以及血管再通后的相似时间段采集动脉血。使用气相色谱和电子捕获检测（GC-ECD）分析血浆中的咪达唑仑、α-羟基咪达唑仑和α-羟基咪达唑仑葡萄糖醛酸苷。六名患者中有五名在无肝期检测到少量但显著的代谢物浓度，表明该药物存在肝外代谢部位。其余一名患者的代谢物血浆浓度低于检测下限（2微克/升）。这可能代表一种药物遗传学异常，或者是由于患者疾病影响肝外代谢部位而导致的咪达唑仑代谢暂时失败。
