The role of human lungs in the biotransformation of propofol.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Human lungs take part in the elimination of propofol by transforming the drug into 2,6-diisopropyl-1,4-quinol.
Dawidowicz
A L
AL
Department of Chemical Physics and Physicochemical Separation Methods, Maria Curie-Sklodowska University, Lublin, Poland. dawid@hermes.umcs.lublin.pl
Fornal
E
E
Mardarowicz
M
M
Fijalkowska
A
A
D018686:Anesthetics, Intravenous / Q000097:blood / Q000493:pharmacokinetics*; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006325:Heart Atria; D006801:Humans; D006873:Hydroquinones / Q000097:blood; D008168:Lung / Q000378:metabolism* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D015742:Propofol / Q000097:blood / Q000493:pharmacokinetics*; D017534:Radial Artery
C414502:2,6-diisopropyl-1,4-quinol; D018686:Anesthetics, Intravenous; D006873:Hydroquinones; D015742:Propofol