Background: The metabolism of the short-acting anaesthetic agent propofol has been described over the first 24 h. However, the long-term disposition of propofol and its metabolites is unclear. We describe the pharmacokinetics (renal excretion rates and renal clearance) of propofol and its metabolites over 60 h.
Methods: Ten patients undergoing lung surgery were included in the study. They received anaesthesia with continuous i.v. propofol at an average rate of 10 mg min(-1). During surgery and 60 h thereafter, we sampled blood and urine. Propofol and its metabolites were measured using gradient high performance liquid chromatography (HPLC).
Results: In nine patients, propofol and its glucuronides were found in the plasma over the first 15 h. In the urine, however, even after 60 h, propofol and its quinol glucuronides were still detectable. One patient had a markedly different pharmacokinetic profile, showing a limited renal excretion or absorption of 12% of the dose.
Conclusions: After an infusion of propofol, patients excrete propofol and its metabolites in the urine over a period in excess of 60 h. We hypothesize that (re)absorption of propofol and its metabolites by the kidney is a major process in elimination and that the reabsorbed compounds are gradually conjugated in the kidney and excreted in the urine. One patient showed a different pharmacokinetic profile for which we currently have no explanation.
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http://dx.doi.org/10.1093/bja/aen134 | DOI Listing |
CNS Drugs
January 2025
Department of Anesthesiology, Jefferson Surgical Center Endoscopy, Sidney Kimmel Medical College, Jefferson Health, 111 S 11th Street, #7132, Philadelphia, PA, 19107, USA.
GABA (γ-aminobutyric acid) receptors are constituents of many inhibitory synapses within the central nervous system. They are formed by 5 subunits out of 19 various subunits: α1-6, β1-3, γ1-3, δ, ε, θ, π, and ρ1-3. Two main subtypes of GABA receptors have been identified, namely GABAA and GABAB.
View Article and Find Full Text PDFNeuropsychiatr Dis Treat
August 2024
Department of Pharmacy, The Second Affiliated Hospital of Soochow University, Suzhou, Jiangsu, People's Republic of China.
Purpose: Parkinson's disease (PD) is a common neurodegenerative disease that severely affects patients' daily lives and places a significant burden on the global economy. There are currently no specific biomarkers for distinguishing between the different stages of PD.
Methods: We divided 78 mice into six equal groups, including five model PD groups (W1-W5; based on the PD stage induced by length of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/propofol induction time) and a control group.
Biochem Pharmacol
November 2024
Laboratory of Pharmacotherapy of Life-Style Related Diseases, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan; Advanced Research Center for Innovations in Next-Generation Medicine, Tohoku University, Sendai 980-8573, Japan; Tohoku Medical Megabank Organization, Tohoku University, Sendai 980-8573, Japan; Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai 980-8574, Japan. Electronic address:
Anesthesiology
August 2024
Departments of Anesthesiology and Critical Care Medicine, Neurology, and Pediatrics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania; Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania.
Background: Unlike expired sevoflurane concentration, propofol lacks a biomarker for its brain effect site concentration, leading to dosing imprecision particularly in infants. Electroencephalography monitoring can serve as a biomarker for propofol effect site concentration, yet proprietary electroencephalography indices are not validated in infants. The authors evaluated spectral edge frequency (SEF95) as a propofol anesthesia biomarker in infants.
View Article and Find Full Text PDFJ Mass Spectrom Adv Clin Lab
April 2024
Department of Anesthesiology, Albany Medical College, Albany, NY, United States.
Introduction: Chromatographic methods for analysis of propofol and its metabolites have been widely used in pharmacokinetic studies of propofol distribution, metabolism, and clearance. Application of chromatographic methods is also needed in clinical and forensic laboratories for detecting and monitoring propofol misuse.
Objective: We report a method for sensitive analysis of propofol, propofol 1-glucuronide (PG), 4-hydroxypropofol 1-glucuronide (1-QG), 4-hydroxypropofol 4-glucuronide (4-QG) and 4-hydroxypropofol 4-sulfate (4-QS) in urine by LC-MS/MS analysis.
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