Hiraoka Haruhiko, Yamamoto Koujirou, Miyoshi Soutarou, Morita Toshihiro, Nakamura Katsunori, Kadoi Yuuji, Kunimoto Fumio, Horiuchi Ryuya
Department of Anaesthesiology, Saitama Cardiovascular and Pulmonary Center, Saitama, Japan.
Br J Clin Pharmacol. 2005 Aug;60(2):176-82. doi: 10.1111/j.1365-2125.2005.02393.x.
The 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.
After 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.
Hepatic 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.
We 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.
丙泊酚代谢的主要部位是肝脏。然而，丙泊酚的全身清除率大于普遍认可的肝血流量。在本研究中，我们通过测量心脏手术患者稳态时的动静脉血药浓度，来确定丙泊酚在肝脏、肺、脑和肾脏中的消除情况。
麻醉诱导后，手术期间持续输注丙泊酚。为测量丙泊酚浓度，在预定时间间隔从桡动脉和肺动脉采集血样。此外，分别在19例植入肝静脉导管的患者和6例植入颈内静脉导管的患者中，同时从肝静脉和颈内静脉采集血样。在19例植入肝静脉导管的患者中，有6例在将导管插入右肾静脉后、插入肝静脉前，同时从桡动脉和肾静脉采集血样。
丙泊酚的肝脏清除率约占全身清除率的60%。丙泊酚的肝提取率为0.87±0.09。桡动脉、肺动脉和颈内静脉之间的丙泊酚浓度无显著差异。然而，观察到肾脏对丙泊酚的提取水平较高——肾提取率为0.70±0.13。
我们已证实在人体中丙泊酚可被肾脏大量提取。肾脏对丙泊酚的代谢清除率几乎占全身清除率的三分之一，可能是该药物肝外消除的主要贡献者。
