Dawidowicz A L, Fornal E, Mardarowicz M, Fijalkowska A
Department of Chemical Physics and Physicochemical Separation Methods, Maria Curie-Sklodowska University, Lublin, Poland.
Anesthesiology. 2000 Oct;93(4):992-7. doi: 10.1097/00000542-200010000-00020.
The metabolism of propofol is very rapid, and its transformation takes place mainly in the liver. There are reports indicating extrahepatic metabolism of the drug, and the alimentary canal, kidneys, and lungs are mentioned as the most probable places where the process occurs. The aim of this study was to determine whether the human lungs really take part in the process of propofol biotransformation.
Blood samples were taken from 55 patients of American Society of Anesthesiologists grade 1-3 scheduled for elective intracranial procedures (n = 47) or for pulmonectomy (n = 8). All patients were premedicated with diazepam (10 mg) administered orally 2 h before anesthesia. Propofol total intravenous anesthesia was performed at the following infusion rates: 12 mg. kg-1. h-1, 9 mg. kg-1. h-1, and 6 mg. kg-1. h-1. Fentanyl and pancuronium bromide were also administered intermittently. After tracheal intubation, the lungs were ventilated to normocapnia with an oxygen-air mixture (fraction of inspired oxygen = 0.33). Blood samples for propofol and 2,6-diisopropyl-1, 4-quinol analysis were taken simultaneously from the right atrium and the radial artery, or the pulmonary artery and the radial artery. The concentration of both substances were measured with high-performance liquid chromatography and gas chromatography-mass spectroscopy.
The concentration of propofol in the central venous system (right atrium or pulmonary artery) is greater than in the radial artery, whereas the opposite is observed for propofol's metabolite, 2,6-diisopropyl-1,4-quinol. Higher propofol concentrations are found in blood taken from the pulmonary artery than in the blood collected from the radial artery.
Human lungs take part in the elimination of propofol by transforming the drug into 2,6-diisopropyl-1,4-quinol.
丙泊酚代谢非常迅速，其转化主要发生在肝脏。有报道指出该药物存在肝外代谢，消化道、肾脏和肺被提及为该过程最可能发生的部位。本研究的目的是确定人类肺部是否真的参与丙泊酚的生物转化过程。
从55例美国麻醉医师协会1 - 3级计划进行择期颅内手术（n = 47）或肺切除术（n = 8）的患者中采集血样。所有患者在麻醉前2小时口服地西泮（10毫克）进行术前用药。丙泊酚全静脉麻醉以以下输注速率进行：12毫克·千克⁻¹·小时⁻¹、9毫克·千克⁻¹·小时⁻¹和6毫克·千克⁻¹·小时⁻¹。还间歇性给予芬太尼和泮库溴铵。气管插管后，用氧气 - 空气混合物（吸入氧分数 = 0.33）使肺通气至正常碳酸血症。同时从右心房和桡动脉或肺动脉和桡动脉采集用于丙泊酚和2,6 - 二异丙基 - 1,4 - 喹啉分析的血样。用高效液相色谱法和气相色谱 - 质谱法测量两种物质的浓度。
丙泊酚在中心静脉系统（右心房或肺动脉）中的浓度高于桡动脉，而丙泊酚的代谢产物2,6 - 二异丙基 - 1,4 - 喹啉则相反。从肺动脉采集的血液中丙泊酚浓度高于从桡动脉采集的血液。
人类肺部通过将丙泊酚转化为2,6 - 二异丙基 - 1,4 - 喹啉参与丙泊酚的消除。
