The fact that total body clearance of propofol metabolism exceeds hepatic blood flow is consistent with extra hepatic clearance.
Indeed hepatic clearance of propofol was approximately 60% of total body clearance.Pulmonary uptake of propofol is significant and influences the initial availability of propofol.
Human lungs take part in the elimination of propofol by transforming the drug into 2,6-diiso-propyl-l,4-quinol.
However, He et al. found that most of the propofol that undergoes pulmonary uptake during the first pass was released back to the circulation by back diffusion without propofol metabolism .
Further evidence was found in the study by Hiraoka et al. They found metabolic clearance of propofol by the kidneys accounts for almost one-third of total body clearance and therefore kidney may be the major contributor to the extrahepatic elimination of this drug.
Therefore, although propofol can be transformed in the lungs to 2,6-diiso-propyl-l,4-quiniol, the amount of drug metabolized is insignificant and therefore, lungs may not be the major site contributing to the extrahepatic propofol metabolism in humans.
Further, extrahepatic glucuronidation in the small intestine and especially in the kidney may contribute to the overall glucuronidation of propofol.
Others found brain as an organ for extrahepatic metabolism of propofol. Therefore, after liver, kidneys play an important role in the elimination of propofol metabolism .