Publications of Raphael DENOOZ
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See detailVariability and target attainment of fluconazole in critically ill patients
Van Daele, Ruth; Wauters, Joost; Brüggemann, Roger J. et al

Poster (2020, April 21)

Background: Fluconazole is an antifungal drug frequently used in the intensive care unit (ICU) but few data are available regarding its exposure in this population. A subanalysis of the DALI-study raised ... [more ▼]

Background: Fluconazole is an antifungal drug frequently used in the intensive care unit (ICU) but few data are available regarding its exposure in this population. A subanalysis of the DALI-study raised some concerns considering variability in exposure and inadequate target attainment in critically ill patients. We aimed to determine fluconazole variability and target attainment at the ICU. Materials/methods: All adult, critically ill patients treated with intravenous fluconazole between May and September 2019 were included, provided that the DNR code was <2 and written informed consent was obtained. The administered dose was left at the discretion of the treating clinician. Trough samples were collected during a maximum period of 15 days. Samples were analysed using an UPLC-DAD analytic method. The intra-and intersubject variability of fluconazole trough concentrations was calculated by dividing the standard deviation by the mean*100. Moreover, the difference between the maximum and minimum fluconazole concentration within each patients was determined. For target attainment, the fAUC/MIC from clinical data amounts to 100 corresponding with trough levels >10-15 mg/L, as recommended by EUCAST and ECIL-6. The limit for toxicity was set on 50 mg/L. Results: Seventeen patients were included, resulting in 95 fluconazole trough levels. Patients had a median APACHE-II score of 18 [16-23] and administered dose of 5.1 [4.1-7.5] mg/kg/day. The median fluconazole trough level was 26.6 [19.7-35.3] mg/L. In Figure 1, fluconazole trough concentrations are depicted in function of the dose. The mean intra-and intersubject variability (CV%) were 18,4% and 34,5%, respectively. The median difference between the maximum and minimum concentration for the 14 patients with >1 measured fluconazole level, was 14,8 [6,6-18,9] mg/L. In two patients, this difference was more than 2-fold. All trough levels were >10mg/L and 85/95 (89%) samples were >15mg/L. None of the levels exceeded the upper limit of 50 mg/L. Conclusions: As shown in the DALI-study, a considerable intra-and intersubject variability in fluconazole levels was observed at the ICU. Despite this variability, all fluconazole trough levels were above the lower limit of 10 mg/L and most of them >15 mg/L. No toxic concentrations were observed. [less ▲]

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See detailProficiency Testing for Meropenem and Piperacillin Therapeutic Drug Monitoring: Preliminary Results From the Belgian Society on Infectiology and Clinical Microbiology Pharmacokinetic-Pharmacodynamic Working Group
Carlier, M.; Athanasopoulos, A.; Borrey, D. et al

in Therapeutic Drug Monitoring (2018), 40(1), 156-158

[No abstract available]

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See detailThe transfer of a high performance liquid chromatography with diode array detection method for the determination in serum of psychotropic drugs
Hahirwa, Innocent; Charlier, Corinne ULiege; Karangwa, Charles et al

in Rwanda Journal (2017), 4(1), 7-16

The relevance of the determination of blood concentration levels of psychotropic drugs has been demonstrated in Rwanda. However, due to the lack of appropriate analytical methods, such activity is not ... [more ▼]

The relevance of the determination of blood concentration levels of psychotropic drugs has been demonstrated in Rwanda. However, due to the lack of appropriate analytical methods, such activity is not carried out in this country. Objective: The aim of this work was to transfer to a Rwandan laboratory a High Performance Liquid Chromatography based method, applicable for the determination in serum of psychotropic drugs commonly prescribed in Rwanda. Method: Liquid-liquid extraction using prazepam as internal standard was used for sample preparation. Chromatographic separation was performed on a Symmetry C8 analytical column, using acetonitrile and a phosphate buffer as mobile phase. The method was validated with respect to total error concept as decision criterion. Results: The validated method was linear over tested dosing intervals with a coefficient of determination greater than 0.99 for all analytes. The precision was good with RSD between 1.3 and 15.6 % and the trueness ranged between 87 and 109 %. The accuracy of the method was demonstrated as well. Conclusion: The analytical method allowing a simultaneous determination in serum of several antipsychotropic drugs was successfully validated and thus transferred to the Laboratory of Analysis of Foodstuffs, Drugs, Water and Toxics (Rwanda). [less ▲]

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See detailStrychnine poisoning still happens in 2015
DEVILLE, Marine ULiege; Lemaire, Eric ULiege; DENOOZ, Raphael ULiege et al

Conference (2016, August 29)

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See detailComparaison et évolution de systèmes de criblage en toxicologie hospitalière
Cohen, S.; Manchon, M.; Allorge, D. et al

in Annales de Toxicologie Analytique (2011, March), 23(1), 1-5

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See detailBlood, urine, and hair kinetic analysis following an acute lead intoxication
KEUTGENS, Aurore ULiege; HO, Giang; SCHOOFS, Roland et al

in Journal of Analytical Toxicology (2011), 35(1), 60-64

A case of lead exposure resulting from the accidental ingestion of a lead-containing solution is reported. Because of clinical management rapidly performed through chelation therapy by 2,3 ... [more ▼]

A case of lead exposure resulting from the accidental ingestion of a lead-containing solution is reported. Because of clinical management rapidly performed through chelation therapy by 2,3-dimercaptopropane sulfonate sodium and meso-2,3-dimercaptosuccinic acid, blood lead levels of this 51-year-old patient were moderate (412.9 μg/L) and no clinical symptoms were observed. Numerous blood and urine samples were collected for kinetic analysis of lead elimination. However, we report the first case in which hair samples were analyzed to determine the excretion level of lead after acute intoxication. [less ▲]

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See detailTOLERANCE INTERVALS AS CONTROL CHART: COMPARISON TO CLASSIC SHEWHART X̅-R CONTROL CHART
Marini Djang'Eing'A, Roland ULiege; Lambert, Véronique; Denooz, Raphael ULiege et al

Poster (2010, September)

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See detailIntérêt clinique et économique du suivi thérapeutique pharmacologique pour des médicaments habituellement non contrôlés
Denooz, Raphael ULiege

Doctoral thesis (2010)

L’objectif principal de ce travail est de démontrer l’intérêt du suivi thérapeutique pharmacologique appliqué à quelques médicaments ou classes pharmaceutiques habituellement non contrôlés. Le suivi ... [more ▼]

L’objectif principal de ce travail est de démontrer l’intérêt du suivi thérapeutique pharmacologique appliqué à quelques médicaments ou classes pharmaceutiques habituellement non contrôlés. Le suivi thérapeutique pharmacologique repose sur la mesure de la concentration sanguine d’un médicament administré à un patient dans le but d’adapter individuellement la posologie. Les deux principales justifications habituellement retenues pour le suivi thérapeutique pharmacologique sont d’une part la diminution du taux d’échecs thérapeutiques, liés à une mauvaise observance ou à l’emploi d’une posologie insuffisante, et d’autre part la réduction de la fréquence des manifestations indésirables et/ou toxiques des médicaments, plutôt associés à une posologie excessive. La liste des médicaments faisant en pratique l’objet de cette démarche est cependant restreinte à une quarantaine de substances, en raison principalement des différents critères qui justifient l’obtention d’une intervention des soins de santé, à savoir : o l’existence d’une corrélation entre la concentration plasmatique et les effets pharmacodynamiques ; o une zone thérapeutique étroite ; o une variabilité pharmacocinétique interindividuelle importante ; o l’absence d’autres marqueurs permettant d’évaluer l’effet thérapeutique. Le but de ce travail est de convaincre les Cliniciens des avantages d’un élargissement de cette liste conventionnelle à d’autres molécules, en leur présentant une multitude d’autres indications pour le suivi thérapeutique pharmacologique, comme la réduction du coût des thérapies antibactériennes par β-lactamines, l’aide au diagnostic d’une résistance ou d’une hypersensibilité aux anticoagulants oraux, l’évaluation des thérapies substitutives par la méthadone, la vérification de la compliance au traitement par sulfonylurées, ou encore la réduction de la toxicité des traitements à base de bupropion et de GHB. Pour répondre à cet objectif, il était nécessaire de développer et de valider plusieurs techniques qui sont en parfaite adéquation avec les besoins du suivi thérapeutique pharmacologique. [less ▲]

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See detailIntérêt du dosage des sulfamidés hypoglycémiants: de la vérification de la compliance au diagnostic différentiel des hyperinsulinismes
Denooz, Raphael ULiege; Charlier, Corinne ULiege

in Revue Médicale de Liège (2010), 65(9), 493-497

Plus de cinquante ans après leur mise sur le marché, les sulfamidés hypoglycémiants font toujours partie du traitement de base du diabète non insulinodépendant. A côté de leurs remarquables propriétés ... [more ▼]

Plus de cinquante ans après leur mise sur le marché, les sulfamidés hypoglycémiants font toujours partie du traitement de base du diabète non insulinodépendant. A côté de leurs remarquables propriétés pharmacologiques, ces produits ont, à différentes reprises, été tenus responsables d’hypoglycémies sévères survenant de manière inexpliquée chez des sujets non diabétiques. Ce type d’hypoglycémie, qualifiée de factice, est notamment fréquemment retrouvée dans le syndrome de Munchausen, trouble psychiatrique poussant le malade à mimer une pathologie. Cette hypoglycémie est associée à un hyperinsulinisme endogène simulant une pathologie endocrine très rare, l’insulinome. Nous souhaitons faire connaître aux Cliniciens l’intérêt de la recherche et du dosage sanguin des sulfamidés hypoglycémiants dans le cadre du diagnostic différentiel des hyperinsulinismes. La mise en évidence d’une hypoglycémie induite par ces médicaments constitue un élément intéressant pour orienter le diagnostic et éventuellement éviter une pancréatectomie en cas de forte suspicion d’insulinome. La méthode analytique développée au laboratoire s’appuie sur la chromatographie liquide ultra performante couplée à la spectrométrie de masse tandem (UPLC -MS -MS ). Par cette technique, on peut mettre en évidence dans le sang une dizaine de sulfonylurées et le répaglinide. Elle constituera à l’avenir une méthode de choix face à toute suspicion de mésusage des sulfonylurées. [less ▲]

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See detailQuantification in postmortem blood and identification in urine of tramadol and its two main metabolites in two cases of lethal tramadol intoxication
De Backer, Benjamin ULiege; Renardy, Françoise ULiege; Denooz, Raphael ULiege et al

in Mitteilungsblatt der Gesellschaft für Toxikologische und Forensische Chemie (2010), 77(3), 252

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See detailMechanisms of Interaction of Endocrine-Disrupting Chemicals with Glutamate-Evoked Secretion of Gonadotropin-Releasing Hormone
Rasier, Gregory ULiege; Parent, Anne-Simone ULiege; Gerard, Arlette ULiege et al

in Toxicological Sciences (2008), 102(1), 33-41

In previous studies, we detected a dichlorodiphenyltrichloroethane (DDT) derivative in the serum of children with sexual precocity after migration from developing countries. Recently, we reported that DDT ... [more ▼]

In previous studies, we detected a dichlorodiphenyltrichloroethane (DDT) derivative in the serum of children with sexual precocity after migration from developing countries. Recently, we reported that DDT stimulated pulsatile gonadotropin-releasing hormone (GnRH) secretion and sexual maturation in the female rat. The aim of this study was to delineate the mechanisms of interaction of endocrine-disrupting chemicals including DDT with GnRH secretion evoked by glutamate in vitro. Using hypothalamic explants obtained from 15-day-old female rats, estradiol (E2) and DDT caused a concentration-related increase in glutamate-evoked GnRH release while p,p'-dichlorodiphenyldichloroethene and methoxychlor had no effect. The effective DDT concentrations in vitro were consistent with the serum concentrations measured in vivo 5 days after exposure of immature rats to 10 mg/kg/day of o,p'-DDT. Bisphenol A induced some stimulatory effect, whereas no change was observed with 4-nonylphenol. The o,p'-DDT effects in vitro were prevented partially by a selective antagonist of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) subtype of glutamate receptors. A complete prevention of o,p'-DDT effects was caused by an estrogen receptor (ER) antagonist as well as an aryl hydrocarbon receptor (AHR) antagonist and inhibitors of protein kinases A and C and mitogen-activated kinases. While an intermittent incubation with E2 caused no change in amplification of the glutamate-evoked GnRH release for 4 h, continuous incubation with E2 or o,p'-DDT caused an increase of this amplification after 3.5 h of incubation. In summary, DDT amplifies the glutamate-evoked GnRH secretion in vitro through rapid and slow effects involving ER, AHR, and AMPA receptor mediation. [less ▲]

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See detailGHB measurement by GC-MS in blood, urine and gastric contents, following an acute intoxication in Belgium
Bodson, Quentin; Denooz, Raphael ULiege; Serpe, Philippe ULiege et al

in Acta Clinica Belgica (2008), 63

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See detailA fatal case of bupropion (ZybanR) overdose
Mercerolle, Magali; Denooz, Raphael ULiege; Lachâtre, Gérard et al

in Journal of Analytical Toxicology (2008), 32

Detailed reference viewed: 178 (56 ULiège)