Literature DB >> 11020752

The role of human lungs in the biotransformation of propofol.

A L Dawidowicz1, E Fornal, M Mardarowicz, A Fijalkowska.   

Abstract

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.

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Year:  2000        PMID: 11020752     DOI: 10.1097/00000542-200010000-00020

Source DB:  PubMed          Journal:  Anesthesiology        ISSN: 0003-3022            Impact factor:   7.892


  9 in total

Review 1.  Propofol: a review of its role in pediatric anesthesia and sedation.

Authors:  Vidya Chidambaran; Andrew Costandi; Ajay D'Mello
Journal:  CNS Drugs       Date:  2015-07       Impact factor: 5.749

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

Authors:  Haruhiko Hiraoka; Koujirou Yamamoto; Soutarou Miyoshi; Toshihiro Morita; Katsunori Nakamura; Yuuji Kadoi; Fumio Kunimoto; Ryuya Horiuchi
Journal:  Br J Clin Pharmacol       Date:  2005-08       Impact factor: 4.335

3.  Free and bound propofol concentrations in human cerebrospinal fluid.

Authors:  Andrzej L Dawidowicz; Rafal Kalitynski; Anna Fijalkowska
Journal:  Br J Clin Pharmacol       Date:  2003-11       Impact factor: 4.335

Review 4.  Propofol for sedation in neuro-intensive care.

Authors:  Michael P Hutchens; Stavros Memtsoudis; Nicholas Sadovnikoff
Journal:  Neurocrit Care       Date:  2006       Impact factor: 3.210

5.  Application of a physiologically based pharmacokinetic model to assess propofol hepatic and renal glucuronidation in isolation: utility of in vitro and in vivo data.

Authors:  Katherine L Gill; Michael Gertz; J Brian Houston; Aleksandra Galetin
Journal:  Drug Metab Dispos       Date:  2013-01-09       Impact factor: 3.922

6.  Human physiologically based pharmacokinetic model for propofol.

Authors:  David G Levitt; Thomas W Schnider
Journal:  BMC Anesthesiol       Date:  2005-04-22       Impact factor: 2.217

Review 7.  Clinical Importance of Potential Genetic Determinants Affecting Propofol Pharmacokinetics and Pharmacodynamics.

Authors:  Ivana Budic; Tatjana Jevtovic Stoimenov; Dimitrije Pavlovic; Vesna Marjanovic; Ivona Djordjevic; Marija Stevic; Dusica Simic
Journal:  Front Med (Lausanne)       Date:  2022-02-28

Review 8.  Metabolic Profiles of Propofol and Fospropofol: Clinical and Forensic Interpretative Aspects.

Authors:  Ricardo Jorge Dinis-Oliveira
Journal:  Biomed Res Int       Date:  2018-05-24       Impact factor: 3.411

Review 9.  Clinical Pharmacokinetics and Pharmacodynamics of Propofol.

Authors:  Marko M Sahinovic; Michel M R F Struys; Anthony R Absalom
Journal:  Clin Pharmacokinet       Date:  2018-12       Impact factor: 6.447

  9 in total

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