Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain
Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain
复制标题
DOI：
10.1111/j.1365-2125.2005.02393.x
复制
发表时间：
2005-08-01
影响因子：
3.4
通讯作者：
Horiuchi, R
中科院分区：
文献类型：
--
作者：
Hiraoka, H;Yamamoto, K;Horiuchi, R
目的异丙酚的主要代谢部位是肝脏。然而，异丙酚的全身清除量大于普遍接受的肝血流量。本研究通过测定心脏手术患者稳态动静脉动静脉血药浓度，确定异丙酚在肝、肺、脑、肾等脏器的排泄。为了测量异丙酚的浓度，每隔一段预定的时间从放射状动脉和肺动脉采集血样。另外，19例置入肝静脉导管的患者和6例置入颈内静脉导管的患者分别同时采集肝静脉和颈内静脉血样。19例置入肝静脉导管的患者中，有6例在置入肝静脉前于右肾静脉插管时，同时采集桡动脉和肾静脉的血样。丙泊酚的肝脏提取比为0.87+/-0.09。异丙酚在放射状动脉、肺动脉和颈内静脉的浓度无显著差异。然而，异丙酚在肾脏中的萃取率很高，肾萃取率为0.70+/-0.13。结论异丙酚在人体内有大量的肾萃取率。异丙酚通过肾脏的代谢清除几乎占全身清除的三分之一，可能是该药物肝外消除的主要原因。
AimsThe principal site for the metabolism of propofol is the liver. However, the total body clearance of propofol is greater than the generally accepted hepatic blood flow. In this study, we determined the elimination of propofol in the liver, lungs, brain and kidneys by measuring the arterial-venous blood concentration at steady state in patients undergoing cardiac surgery.MethodsAfter induction of anaesthesia, propofol was infused continuously during surgery. For measurement of propofol concentration, blood samples were collected from the radial and pulmonary artery at predetermined intervals. In addition, blood samples from hepatic and internal jugular vein were collected at the same times in 19 patients in whom a hepatic venous catheter was fitted and the other six in whom an internal jugular venous catheter was fitted, respectively. In six out of 19 patients fitted with a hepatic venous catheter, blood samples from the radial artery and the renal vein were also collected at the same time, when the catheter was inserted into the right renal vein before insertion into the hepatic vein.ResultsHepatic clearance of propofol was approximately 60% of total body clearance. The hepatic extraction ratio of propofol was 0.87 +/- 0.09. There was no significant difference in the concentration of propofol between the radial, pulmonary arteries and internal jugular vein. However, a high level of propofol extraction in the kidneys was observed - the renal extraction ratio being 0.70 +/- 0.13.ConclusionsWe have demonstrated substantial renal extraction of propofol in human. Metabolic clearance of propofol by the kidneys accounts for almost one-third of total body clearance and may be the major contributor to the extrahepatic elimination of this drug.