Kidneys contribute to the extrahepatic clearance of propofol in humans, but not lungs and brain.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Hiraoka
Haruhiko
H
Department of Anaesthesiology, Saitama Cardiovascular and Pulmonary Center, Saitama, Japan.
Yamamoto
Koujirou
K
Miyoshi
Soutarou
S
Morita
Toshihiro
T
Nakamura
Katsunori
K
Kadoi
Yuuji
Y
Kunimoto
Fumio
F
Horiuchi
Ryuya
R
D000328:Adult; D000368:Aged; D018686:Anesthetics, Intravenous / Q000493:pharmacokinetics*; D001921:Brain / Q000378:metabolism*; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism*; D008168:Lung / Q000378:metabolism*; D008297:Male; D008657:Metabolic Clearance Rate; D008875:Middle Aged; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics*; D011651:Pulmonary Artery; D017534:Radial Artery; D012077:Renal Artery
D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D015742:Propofol