Urinary propofol metabolites in early life after single intravenous bolus

Allegaert, Karel; Vancraeynest, Julie; Rayyan, Maissa; Hoon, Jan de; Cossey, Veerle; Naulaers, Gunnar; Verbesselt, René

doi:10.1093/bja/aen276

Cited by 26 publications

(14 citation statements)

References 20 publications

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“…Subsequently they were gradually excreted. Urinary excretion profiles of propofol and PG were quite consistent with previous reports [7,12,13]. Table 1 Comparison of GC/MS and LC-ESI-MS methods for the analysis of propofol and its metabolites in human urine.…”

Section: Analysis Of Propofol and Its Metabolites By Lc/mssupporting

confidence: 86%

“…The LLOQs for propofol-TMS and PG obtained by GC/MS-SIM mode and LC/MS-MRM mode, respectively, were about 0.51 and 2.01 ppb. These LLOQs were over two orders lower than those reported previously [9,12,13]. The correlation coefficients for the calibration curves of propofol and PG were over 0.995 and 0.990, respectively, indicating good linearity.…”

Section: Analysis Of Propofol and Its Metabolites By Lc/msmentioning

confidence: 46%

“…However, phase I and II metabolites of propofol could not be successfully extracted simultaneously by the SPE or LLE methods because of significant differences in the chemical properties between the lipophilic phase I metabolites including the parent drug and the hydrophilic phase II metabolites. Therefore, we used a previous reported sample treatment for LC/MS analysis [7,13,14] that relies on a very simple centrifugation and dilution. In the present study, we used a centrifugation and dilution in 1:29 methanol/water (1:1, v/v) which provided rapidity and convenience in the sample workup and showed the satisfactory extraction yields without any significant loss of analytes.…”

Section: Sample Preparation For Gc/ms and Lc/ms Analysismentioning

confidence: 99%

“…Various analytical methods have been reported for the determination of propofol and its metabolites in biological matrices such as blood [9][10][11], urine [8,[12][13][14] and hair [15] including the use of high performance liquid chromatography (HPLC) with UV detection [4,7], and gas chromatography coupled mass spectrometry (GC/MS) [14,15]. In general, GC/MS methods have been used for the determination of propofol and its metabolites on account of the high separation capacity and detection sensitivity of the volatile compounds, even though intensive sample workup such as extraction and derivatization is required [14,16].…”

Section: Introductionmentioning

confidence: 99%

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Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine

Lee

Park

Jeong

et al. 2012

Journal of Chromatography B

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Section: Analysis Of Propofol and Its Metabolites By Lc/mssupporting

confidence: 86%

Section: Analysis Of Propofol and Its Metabolites By Lc/msmentioning

confidence: 46%

Section: Sample Preparation For Gc/ms and Lc/ms Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine

Lee

Park

Jeong

et al. 2012

Journal of Chromatography B

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“…Based on population PK analyses, overall propofol clearance is lower in neonates compared with adults, displays large variability with hydroxylation as most important route, and with postmenstrual age (PMA) as the most relevant covariate. In addition, a postnatal age (PNA) of 10 days was defined as a time point after which glucuronidation capacity increases [1,10,11]. As mentioned before, populationspecific diseases like indirect hyperbilirubinemia could not be retained as a relevant biomarker of reduced propofol clearance in neonates, and the same holds true for gender [2].…”

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confidence: 99%

Biomarkers of Propofol Metabolism in Neonates: The Quest Beyond Ontogeny

2017

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" We anticipate that the contribution of genetic variants will be different in neonates comparedwith adults, since ontogeny of the metabolizing enzymes has to be taken into account "First draft submitted: 1 June 2017; Accepted for publication: 11 July 2017; Published online: 23 October 2017The use of propofol, a short-acting sedative, for procedural sedation in neonates is increasing. In early life, a remarkable variability in propofol clearance has been documented. At present, two-third of this variability can be explained by age [1]. Although the impact of indirect hyperbilirubinemia as biomarker of reduced propofol clearance in neonates was explored, it was not retained as relevant clinical predictor [2]. Since in the last few years, no additional covariates of propofol pharmacokinetics (PK) and/or pharmacodynamics (PD) have been documented in neonates, it might be useful to determine whether covariates defined in other populations are relevant to be explored in neonates or not. Starting with a summary of covariates contributing to propofol PK/PD variability in adults, we reflect on the current knowledge of propofol disposition in neonates, and on future challenges to further explore covariates explaining neonatal propofol disposition.As a highly lipophilic compound, propofol immediately distributes to the subcutaneous fat and central nervous system after intravenous administration. In adults, 90% of the propofol dose is metabolized in the liver, and the metabolites are excreted in urine. Both Phase I (hydroxylation) and Phase II (glucuronidation) processes contribute to propofol metabolism. In adults, 70% is converted to propofol glucuronide by uridine diphosphate UGT1A9, while the CYP2B6 and to a lesser extent, CYP2C9 are responsible for the hydroxylation of propofol to 1-and 4-quinol metabolites. These metabolites subsequently undergo glucuronidation or sulfation [3]. The large intersubject variability in propofol biotransformation in adults is in part attributed to patient-related characteristics (i.e., age, weight, height, lean body mass, gender and genetic polymorphisms), disease state and environmental factors.Choong et al. documented the impact of gender in adults receiving propofol by target-controlled infusion for elective surgery. Significantly higher area under the curve values of the hydroxyl and glucuronide metabolites were observed in women [4]. This suggests a dimorphic propofol metabolism in vivo, with higher metabolic turnover in female compared with male subjects. Their findings confirmed results of a previous pilot study as well as in vitro data [5]. In their pilot study, higher (i.e., 1.7 to 2.1-fold difference) weight-corrected area under the curve for all propofol glucuronides after a single propofol bolus were found in women compared with men [5]. Also in an elderly cohort (65-91 years), the impact of gender on propofol PK was observed by Vuyk et al. Predicted propofol concentrations during continuous infusion (i.e., 1.5 mg/kg propofol bolus in 1 min followed by 7 mg/kg/h for 89 min) w...

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Propofol for procedural sedation/anaesthesia in neonates

Shah

2011

Cochrane Database of Systematic Reviews

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Urinary propofol metabolites in early life after single intravenous bolus

Cited by 26 publications

References 20 publications

Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine

Comparison of GC/MS and LC/MS methods for the analysis of propofol and its metabolites in urine

Biomarkers of Propofol Metabolism in Neonates: The Quest Beyond Ontogeny

Propofol for procedural sedation/anaesthesia in neonates

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