Modelled Target Attainment after Temocillin Treatment in Severe Pneumonia: Systemic and Epithelial Lining Fluid Pharmacokinetics of Continuous versus Intermittent Infusions.

The objective of this article is to describe the population pharmacokinetics (PK) of temocillin administered via continuous infusion (CI) versus intermittent infusion (II) in critically ill patients with pneumonia. Secondary objectives included characterization of epithelial lining fluid (ELF)/plasma penetration ratios and determination of the probability of target attainment (PTA) for a range of MICs. Thirty-two mechanically ventilated patients who were treated for pneumonia with 6 g of temocillin daily for sensitive pathogens were assigned to either the II (2 g every 8 h over 0.

Pharmacokinetic Variability and Target Attainment of Fluconazole in Critically Ill Patients.

: Fluconazole is one of the oldest antifungal drugs. Previous studies have raised concerns considering variability in exposure and inadequate target attainment in critically ill patients. The current study aims to define variability and target attainment for fluconazole exposure in a large group of critically ill patients.

Continuous infusion of cefepime and neurotoxicity: a retrospective cohort study.

Objectives: Neurotoxicity related to cefepime is increasingly reported in the literature but specific data concerning continuous infusion (CI) of the drug are still lacking. Our primary objective was to evaluate the incidence of neurotoxicity related to CI of cefepime and the associated risk factors. Our secondary objectives were to analyse the plasma cefepime concentrations and to define the threshold above which neurotoxicity occurs.

Validation of an UHPLC/DAD method for the determination of cannabinoids in seized materials: Analysis of 213 samples sold in Belgian CBD shops.

Purpose: Nowadays, (-)-cannabidiol (CBD) is gaining popularity for the treatment of various problems and can be found easily in many stores in Belgium. However, such product must comply with the law: if the total tetrahydrocannabinol (THC) content [(-)-Δ9-tetrahydrocannabinol + (-)-Δ9-tetrahydrocannabinolic acid A (THC-A)] is higher than 0.2%, it is considered as narcotic by the Belgian legislation.

[Biological markers of alcohol consumption].

To recognize an alcoholic subject is a frequent request, in a medical or forensic setting. The reasons to determine the alcoholic status of an individual are many and various. Amongst the most frequent are : to decide on the origin of liver or neurological disease, put and maintain a liver transplantation candidate on a waiting list, identify the alcoholic worker to prevent work-related accidents, or evaluate the possible risk an alcoholic individual represents, for road safety or for parental custody.

Site-, Technique-, and Time-Related Aspects of the Postmortem Redistribution of Diazepam, Methadone, Morphine, and their Metabolites: Interest of Popliteal Vein Blood Sampling.

Sampling site, technique, and time influence postmortem drug concentrations. In 57 cases, we studied drug concentration differences as follows: subclavian vein-dissection/clamping versus blind stick, femoral vein-dissection/clamping versus blind stick, right cardiac chamber, and popliteal vein-dissection and clamping only. Cases were distributed in group #1 (all cases with both techniques), group #2 (dissection/clamping), and group #3 (blind stick).

Postmortem Concentration and Redistribution of Diazepam, Methadone, and Morphine with Subclavian and Femoral Vein Dissection/Clamping.

Postmortem redistribution (PMR) concerns blood drug concentration variations after death, depending on many factors such as sampling site and technique. In our study, we focused on sampling method. 30 cases were sampled, each at cardiac, subclavian, femoral, and popliteal sites.

Popliteal Vein Blood Sampling and the Postmortem Redistribution of Diazepam, Methadone, and Morphine.

Postmortem redistribution (PMR) refers to the site- and time-related blood drug concentration variations after death. We compared central blood (cardiac and subclavian) with peripheral blood (femoral and popliteal) concentrations of diazepam, methadone, and morphine. To our knowledge, popliteal blood has never been compared with other sites.

Determination of blood concentration levels of psychotropic medications in Rwandan patients.

Objectives: In Rwanda, no therapeutic monitoring of psychotropic drugs is done. This results in difficult treatment optimisation and exposition to a high risk of toxicity and drug ineffectiveness for patients under treatment. This study aimed to determine blood concentration levels of psychotropic drugs in Rwandan patients and identify problems associated with the lack of therapeutic drug monitoring (TDM) of these drugs.

Modelled target attainment after meropenem infusion in patients with severe nosocomial pneumonia: the PROMESSE study.

Objectives: The objective of this study was to propose an optimal treatment regimen of meropenem in critically ill patients with severe nosocomial pneumonia.

Patients And Methods: Among 55 patients in intensive care treated with 1 g of meropenem every 8 h for severe nosocomial pneumonia, 30 were assigned to intermittent infusion (II; over 0.5 h) and 25 to extended infusion (EI; over 3 h) groups.

Simultaneous determination of seven azole antifungal drugs in serum by ultra-high pressure liquid chromatography and diode array detection.

Azole antifungals are a group of fungistatic agents that can be administered orally or parenterally. The determination of the concentrations of these antifungals (miconazole, fluconazole, ketoconazole, posaconazole, voriconazole, itraconazole, and its major active metabolite, hydroxy-itraconazole) in serum can be useful to adapt the doses to pharmacological ranges because of large variability in the absorption and metabolism of the drugs, multiple drug interactions, but also potential resistance or toxicity. A method was developed and validated for the simultaneous determination of these drugs in serum utilizing ultra-high pressure liquid chromatography and diode array detection (UHPLC-DAD).

Identification and structural elucidation of four cannabimimetic compounds (RCS-4, AM-2201, JWH-203 and JWH-210) in seized products.

Since 2008, herbal mixtures with synthetic cannabinoid compounds have been sold as incense throughout the world. Although these new drugs are labeled as not for human consumption, these products are smoked for their cannabis-like effects. This study reports the structural and spectral elucidation of four cannabimimetic compounds seized in Belgium: (4-methoxyphenyl)-1-(pentyl-1H-indol-3-yl)methanone (RCS-4), 1-(5-fluoropentyl)-3-(1-naphtoyl)indole (AM-2201), 2-(2-chlorophenyl)-1-(1-pentylindol-3-yl)ethanone (JWH-203) and 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210).

Blood, urine, and hair kinetic analysis following an acute lead intoxication.

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.

[Sulfonylureas dosage: from therapeutic monitoring to differential diagnosis of hyperinsulinism].

More than fifty years after their marketing, sulfonylureas remain one of the most prescribed drugs for the treatment of non-insulino-dependent diabetes mellitus. However, these products are sometimes responsible of unexplained and severe hypoglycaemias observed in patient without diabetic pathology. These typical hypoglycemias, qualified as factious, are one of the clinical expressions of the Munchausen syndrome, a psychiatric disorder characterized by the need for the subject to simulate a pathology.

Quantification in postmortem blood and identification in urine of tramadol and its two main metabolites in two cases of lethal tramadol intoxication.

Tramadol is an opioid analgesic considered to induce fewer side effects than other compounds of this class. It has been extensively prescribed for two decades. However, serious complications may occur in case of intoxication.

Ultra-performance liquid chromatography- tandem mass spectrometry method for the determination of bupropion and its main metabolites in human whole blood.

A selective and sensitive ultra-performance liquid chromatography (UPLC)-electrospray ionization-tandem mass spectrometry (MS) method for simultaneous determination of bupropion and its main metabolites, hydroxybupropion, erythrohydrobupropion, and threohydrobupropion, in human whole blood is presented. The sample preparation consists of cleanup protein precipitation with methanol combined with a solid-phase extraction on Oasis HLB cartridges. Analytes were separated on a Waters Acquity UPLC((R)) BEH phenyl column using a binary mobile phase consisting of ammonium formate buffer (2 mM, pH 4) and acetonitrile.

Combined pharmacokinetic and urodynamic study of the effects of oral administration of phenylpropanolamine in female Beagle dogs.

This study investigated the differences in pharmacokinetic, urodynamic and haemodynamic parameters after administration of two dosages of phenylpropanolamine (PPA) in female Beagle dogs. Blood was collected and urethral pressure profiles were performed over 24 h periods following single or three times daily (T(0),T(6h),T(12h)) administration of PPA. The maximal concentration (C(max)) was reached 2 h after PPA administration (T(max)) and the half-life (T((1/2))) was 4 h.

Fatal intoxications by acenocoumarol, phenprocoumon and warfarin: method validation in blood using the total error approach.

A simple high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection has been developed and validated for simultaneous identification and quantification of three antivitamin K drugs (acenocoumarol, warfarin and phenprocoumon) in whole blood. The aim of this development was to propose an analytical technique adapted to the situations of forensic toxicology, i.e.

Gamma-hydroxybutyric acid (GHB) measurement by GC-MS in blood, urine and gastric contents, following an acute intoxication in Belgium.

Gamma-hydroxybutyrate (GHB, sodium oxybate) is a compound related to neuromodulator gamma-aminobutyric acid (GABA), emerging as a recreational drug of abuse and as a rape drug. GHB-related emergencies have dramatically increased in the 1990s, but a decrease is observed since 2000. We describe the case of an acute GHB intoxication in a 28-year-old male who fell unconscious after ingestion of a mouthful of an unknown beverage, and required medical support for 2 days.

Skin protection creams in medical settings: successful or evil?

Background: Chronic exposure to mild irritants including cleansing and antiseptic products used for hand hygiene generates insults to the skin. To avoid unpleasant reactions, skin protection creams are commonly employed, but some fail to afford protection against a variety of xenobiotics. In this study, two skin protection creams were assayed comparatively looking for a protective effect if any against a liquid soap and an alcohol-based gel designed for hand hygiene in medical settings.

A fatal case of bupropion (Zyban) overdose.

A sensitive and reproducible method for the identification and the quantitative determination of bupropion (BUP) and its major metabolites, hydroxybupropion (OH-BUP) and threohydrobupropion (T-BUP), was developed in blood and urine. The three compounds were extracted with a solid-phase extraction procedure followed by LC-ESI-MS-MS separation and quantification using decadeuterated lidocaine as internal standard. BUP and its metabolites were satisfactorily identified by multiple reactions monitoring detection.

Simultaneous determination of five beta-lactam antibiotics (cefepim, ceftazidim, cefuroxim, meropenem and piperacillin) in human plasma by high-performance liquid chromatography with ultraviolet detection.

Monitoring of plasma antibiotic drugs is useful for better clinical management in infected patients, particularly in intensive care units. A simple and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection has been developed and validated for simultaneous quantification of five beta-lactam antibiotics in human plasma: cefepim, ceftazidim, cefuroxim, meropenem and piperacillin. The plasma sample, after spiked with ceforanid as an internal standard (IS), was submitted to a solid-phase extraction (SPE) prior to HPLC analysis.

Mechanisms of interaction of endocrine-disrupting chemicals with glutamate-evoked secretion of gonadotropin-releasing hormone.

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.