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Aims We aimed at assessing the effectiveness of renal replacement therapy in patients severely self-poisoned with baclofen and with normal kidney function. Methods A population pharmacokinetic model was built using analytical data extracted from 26 baclofen poisoning cases reported to a French Poison Centre: 8 patients underwent renal replacement therapy (RRT), 18 did not. In the RRT group, 2 patients suffered from kidney failure. Mechanical ventilation was required for 20 patients with normal kidney function; 15 were not treated by RRT and 5 were. Pharmacokinetic profiles of baclofen were measured in 28 patients and further modelled by a non-parametric approach (PMetrics®). The total data set was divided into a building data set (26 patients, 57 observations) and a validation set (2 external patients, 6 observations). Then, the estimated elimination half-life of baclofen and the duration of intubation were compared in patients with or without RRT using Wilcoxon–Mann–Whitney test. Results A model using three parameters plus a lag time and bioavailability was necessary to determine the pharmacokinetics of baclofen. Estimated elimination half-life in the ‘RRT’ group and the ‘no RRT’ group were respectively 3.1 [2.2−4.8] h (n = 6 patients) and 3.4 [1.4−5.5] h (n = 19 patients, p = 0.53). The median duration of intubation was not significantly different between groups (72 [48−72] h and 72 [24−96] h, respectively; p = 0.38). Conclusion Renal replacement therapy did not appear to significantly increase baclofen clearance in patients without kidney failure.

Levamisole is a drug originally prescribed as an antihelmintic. Because of the occurrence of severe cases of agranulocytosis and leukoencephalitis it was removed from the French market in 1998 for human use, while it remains available for veterinary use. Nowadays in France its only use in humans is regulated by authorization for temporary use for its immunomodulatory properties in the treatment of nephritic syndrome. A 52-year-old man was found dead at his farm. Injection points were observed on his arm and a syringe containing a dark orange-brown liquid was found near the body. At his home, the discovery of a letter highlighted suicidal intent. Analysis of the aforementioned liquid, peripheral blood and urine confirmed the unique presence of levamisole. The femoral blood concentration of levamisole was of 25 mg/L whereas the femoral blood concentrations reported in cases of fatalities after cocaine use do not exceed 0.0056 mg/L. In humans, levamisole can be detected in biological samples after cocaine use as this drug is also an adulterant and one of its metabolites (aminorex) seems to have amphetamine-like properties. In this case, the man consumed levamisole from time to time for its stimulant and strengthening effects. Cases of fatal poisoning using levamisole are very rare and poorly documented, which makes the interpretation of postmortem blood levamisole concentration difficult.

Resume Contexte et objectifs A la demande de la Direction generale de la sante, la Haute Autorite de sante (HAS), en partenariat avec la Societe de toxicologie clinique (STC) et avec la collaboration de la Societe francaise de medecine du travail (SFMT), la Societe francaise de sante publique (SFSP), la Societe francaise de toxicologie analytique (SFTA) et la Societe francophone de sante-environnement (SFSE) a elabore des recommandations pour le depistage des surexpositions environnementales a l’arsenic inorganique (Asi) et la prise en charge des populations concernees. Methode La methode d’elaboration utilisee est celle des Recommandations pour la pratique clinique (RPC) de la HAS (HAS, 2010). Resultats Les recommandations elaborees identifient : les sites susceptibles d’entrainer des surexpositions environnementales, a partir de la concentration d’Asi dans leur sol ; la fraction des residents qui constitue la population cible du depistage ; les modalites de ce depistage qui utilise le dosage de l’Asi et de ses metabolites dans les urines. En fonction des resultats du primo-depistage, elles precisent les indications et le deroulement de la surveillance biometrologique. Elles indiquent la fraction de la population exposee qui constitue la cible de la recherche de complications de la surexposition environnementale a l’Asi. Elles precisent les modalites de cette recherche. Enfin, elles proposent des mesures pour le traitement et la prevention des contaminations par l’Asi de l’environnement.

Summary Paliperidone (9-hydroxyrisperidone), the primary active metabolite of risperidone, is a benzisoxazole derivative of the second-generation antipsychotics. Paliperidone palmitate or PP (the palmitate ester of paliperidone) is available as a once-daily oral tablet, a once-monthly injection or PP1M, and a 3-monthly injection or PP3M (marketed under the name of Trevicta® in the European Union). Despite the recent availability of PP3M, several cases of intoxication have been reported worldwide, including lethal cases. However, in Europe, no case of fatal poising has been reported to date. A 33-year-old man was found dead in his room at his parents’ home. His only medical background was a history of schizophrenia. The external examination was without any particularity except a runny nose of brownish liquid with an alcoholic smell. Given the context and the lack of evidence of a third party intervention, an autopsy was not considered necessary. Toxicological analysis of right femoral blood highlighted the presence of paliperidone (240 μg/L) only. The risk associated with the use of PP3M formulation is still imperfectly evaluated and several cases of intoxication have been reported worldwide, including fatal cases. In this case, paliperidone poisoning appears to be the highly likely cause of death. In fact, the blood concentration of paliperidone is high, twice the toxicity threshold used in therapeutic monitoring, and no other substances have been identified. This case highlights: the necessity to always evaluate the benefit-risk balance when prescribing this sustained-release form of paliperidone and the difficulties in interpreting paliperidone concentration in forensic cases.

In developed countries, lead intoxication is decreasing in adults as sources of contamination were considerably reduced. Hence, cases of lead encephalopathy have become scarcer. We report the case of a 50-year-old woman who developed a systemic intoxication due the persistence of lead fragments in her abdomen and back. The patient was shot with homemade gun bullets, which were immediately surgically removed. During the eight following months, she presented progressive worsening signs of systemic and cerebral lead intoxication. On admission to hospital, her blood lead concentration was of 1650 µg/L. Despite surgeries and the use of lead chelators, she died 8 days later. Organs were harvested during postmortem autopsy for pathological investigations, and cerebral lead concentration was determined using inductively coupled plasma–mass spectrometry. Lead encephalopathy was confirmed based on elevated lead concentration measured in brain (3.04 µg/g in cortex and 2.70 µg/g in nucleus lentiformis). Furthermore, neuropathological examination highlighted a strong blood brain barrier (BBB) disruption. Based on this fatal lead intoxication case, it appears that BBB leakage is a major pathological sign of lead encephalopathy and that lead titration in formalin-fixed brain tissue is a valuable tool for diagnosis.

Resume L'issue des grossesses apres chirurgie bariatrique semble favorable, avec une reduction de l'incidence du diabete gestationnel, des troubles hypertensifs et de la macrosomie. Neanmoins, une augmentation de l'incidence des nouveau-nes de petit poids pour l'âge gestationnel et de la prematurite est constatee. Des carences nutritionnelles de severite variable pour la mere et le nouveau-ne et des complications chirurgicales de pronostic potentiellement severe sont observees. Notre groupe de travail multidisciplinaire propose des recommandations elaborees selon la methodologie de la Haute Autorite de sante (HAS) et concernent les questions suivantes : delai entre chirurgie et grossesse, choix de contraception, technique chirurgicale privilegiee pour les femmes en âge de procreer, specificite du parcours obstetrical, modalites de depistage des carences et supplementations nutritionnelles, depistage et gestion du diabete gestationnel, prise de poids optimale, serrage de l'anneau gastrique, conduite a tenir devant une suspicion d'urgence chirurgicale, soins specifiques pendant la periode post-partum et pour les nouveau-nes.

L’évolution des grossesses après chirurgie bariatrique apparaît favorable avec une diminution des risques de diabète gestationnel, d’hypertension et de macrosomie fœtale, mais une augmentation des risques de petit poids de naissance pour l’âge gestationnel et de prématurité des nouveau-nés. Sont également reportées des carences nutritionnelles plus oumoins sévères chez les mères et les nouveau-nés, ainsi que des complications chirurgicales de pronostic parfois défavorable. BARIA-MAT est un groupe de travail multidisciplinaire, proposant des recommandations de bonnes pratiques cliniques, élaborées selon la méthodologie de la Haute Autorité de santé. Les questions abordées par le groupe ont inclus : délai entre chirurgie et grossesse, choix de contraception, technique chirurgicale privilégiée pour les femmes en âge de procréer, spécificité du parcours obstétrical, modalités de dépistage des carences et supplémentations nutritionnelles, dépistage et gestion du diabète gestationnel, prise de poids optimale, ajustement de l’anneau gastrique, conduite à tenir devant une suspicion d’urgence chirurgicale, soins spécifiques pendant la période post-partum et pour les nouveau-nés.

International audience; Although old molecules, alkylating agents and platinum derivatives are still widely used in the treatment of various solid tumors. However, systemic toxicity and cellular resistance mechanisms impede their efficacy. Innovative strategies, including local administration, optimization of treatment schedule/dosage, synergistic combinations, and the encapsulation of bioactive molecules in smart, multifunctional drug delivery systems, have shown promising results in potentiating anticancer activity while circumventing such hurdles. Furthermore, questioning of the old paradigm according to which nuclear DNA is the critical target of their anticancer activity has shed light on subcellular alternative and neglected targets that obviously participate in the mediation of cytotoxicity or resistance. Thus, rethinking of the use of these pivotal antineoplastic agents appears critical to improve clinical outcomes in the management of solid tumors.

International audience

Background High‐dose chemotherapy (HDCT) with TI‐CE regimen is a valid option for the treatment of relapsed advanced germ cell tumors (GCT). We report a phase II trial with therapeutic drug monitoring of carboplatin for optimizing area under the curve (AUC) of this drug. Methods Patients with unfavorable relapsed GCT were treated according to TI‐CE regimen: two cycles combining paclitaxel and ifosfamide followed by three cycles of HD carboplatin plus etoposide administered on 3 days. Carboplatin dose was adapted on day 3 based on carboplatin clearance (CL) at day 1 in order to reach a target AUC of 24 mg.min/mL per cycle. The primary endpoint was the complete response (CR) rate. Results Eighty‐nine patients who received HDCT were included in the modified intent‐to‐treat (mITT) analysis. Measured mean AUC was 24.4 mg.min/mL per cycle (22.4 and 26.8 mg.min/mL for 10th and 90th percentiles). Thirty‐five (44.3%) patients achieved a CR with or without surgery of residual masses and 20 patients achieved a partial response with negative tumor markers. With a median follow‐up of 44 months (m), median PFS was 12.3 m (95% CI: 7.5–25.9) and OS was 46.3 m (95% CI: 18.6–not reached). For high‐ and very high‐risk patients, according to the International Prognostic Score at first relapse or treated after at least one salvage treatment (n = 51), 2‐year PFS rate was 41.1%. Conclusion The rates of complete and favorable responses were clinically relevant in this very poor risk population. Individual monitoring of carboplatin plasma concentration permitted to control more accurately the target AUC and avoided both underexposure and overexposure to the drug., The superiority of HDCT over standard chemotherapy as initial salvage treatment of patients with relapsed or refractory germ cell tumors remains a valid question. In the TI‐CE regimen, TDM was demonstrated to be feasible in routine practice and really allowed to control target AUC more accurately compared to previous reports, avoiding both underexposure and overexposure to carboplatin. In our study, the rate of CR observed in this population with very poor prognosis was 44.3% and increased to 69.6% of favorable responses. Based on our study and if the benefit of HDCT is proven in the TIGER trial, we suggest that the use of carboplatin TDM for dose individualization in current practice should be considered.

Objectives Occupational exposure to molybdenum has been poorly documented to date. Here, we present a retrospective study evaluating urinary molybdenum concentration before and after shift over a period of 2 years in exposed workers. Methods This retrospective study was conducted across eight industrial sites in France and included all workers undergoing medical follow-up for occupational molybdenum exposure. A mean of six sequential samples (before and after shift) was performed for each worker. The urinary molybdenum concentration was determined using a validated method of inductively coupled plasma-mass spectrometry. A mixed linear model was built and linear regression was used to verify the extent to which the urinary molybdenum concentration depends on the age of the workers and the sampling period. Additionally, an analysis based on individual trajectory was also performed. Results Seventy-seven workers were included in the present study. Post-shift urinary molybdenum concentrations were significantly higher than pre-shift values [median (95th percentile) 37.9 (91.1), versus 60.6 (190.0) µg g−1 creatinine, respectively, P < 0.009]. No accumulation of molybdenum over time was observed. The urinary molybdenum concentrations were not influenced by age. Four workers presented high post-shift values as a result of not adhering to protection measures (maxima of 529.8, 359.7, 386.3, and 1459.7 µg g−1 creatinine, respectively). Conclusions To our knowledge, this is the first study of occupational molybdenum exposure in France to include an individual trajectory analysis. No accumulation of molybdenum was seen but high post-shift molybdenum urinary concentrations were observed for some workers. The study emphasizes the importance of molybdenum monitoring in exposed workers.

Background In France, the prevalence of childhood lead poisoning is becoming rare since the avoidance of lead in paints in 1949 and the gradual replacement of water pipes. Chronic lead toxicity is well known and is well correlated to blood lead concentration. Aim Here we report a case of severe lead poisoning occurring in a young female child with a pica behavior. Methods A blood sample and four environmental samples were analyzed using inductively coupled plasma- mass spectrometry (ICP-MS). Lead concentration, lead isotopes and elemental ratios were compared. Results The determination of 208Pb/206Pb, 206Pb/207Pb and Cd/Pb has allowed us to identify the origin of lead poisoning. Discussion-conclusion The source of contamination was eliminated and the child benefited from a psychological and medical follow up. Her outcome was positive. This case illustrated the potential interest of the use of elemental and isotopic ratios for clinical practice as the ICP-MS measurement has allowed a quick response and a rapid eviction of the contamination’s source.

Background Silver is used in various industrial applications, but also in confectioneries and for therapeutic use due to its antibiotic properties. Its toxicity is not well documented and most often only in the context of professional exposure. Aim Here we report two cases of high silver concentrations in biological samples in two women: the first patient presented grey marks around her cuticles, probably due to her consumption of silvered sweets and the second patient presented agranulocytosis and thrombocytopenia occurring within 24 h after the topical application of a cream containing sulfadiazine and silver to burns over a large surface area. Methods Silver concentrations were determined in blood and urine samples and sweets using inductively coupled plasma- mass spectrometry (ICP-MS). Results The silver concentrations were elevated compared to population reference values and confirmed the hypotheses for the patients: the significant consumption of sweets coated with silver nanoparticles and the topical application of a cream containing silver to burns over a large area. Discussion-conclusion After initial questioning by the dermatologist, Patient 1 explained that she consumed more than 30 bags of the sweets per year. She decreased her consumption of the sweets and the control performed one year later showed a plasma silver concentration of 1.5 μg/L. For Patient 2, the absorption of silver through burns over a large area appeared relatively significant, whereas it is very low through undamaged skin. The haematological cells counts returned to normal levels quickly and no other major effects were highlighted. To apply these findings to a larger population, further investigation to determine sulfadiazine and silver concentrations in plasma and urine have been initiated in a cohort of patients with burns over a large area.

Objective The objectives were to define the maximum tolerated dose (MTD), safety profile and pharmacokinetics (PKs) of intraperitoneal oxaliplatin delivered by pressurised intraperitoneal aerosol chemotherapy (PIPAC) in patients with advanced peritoneal carcinomatosis from gastrointestinal tract cancers. Methods PIPAC was applied every 4–6 weeks, for 5 cycles, in a phase I dose-escalation study using a 3 + 3 design. The first dose level was 90 mg/m2 with planned increases of 50 mg/m2 per level. Platinum concentration was measured in plasma, tissues and intraperitoneal fluid samples. The trial was registered at ClinicalTrials.gov ( NCT03294252 ). Results Ten patients with 33 PIPAC sessions were included. No dose limiting toxicity (DLT) occurred at 90 mg/m2 and two at 140 mg/m2. The MTD was therefore set at 90 mg/m2. Overall treatment included a median number of three PIPAC sessions (range: 1–5) and secondary complete cytoreductive surgery for two patients. Overall safety showed 67 grade I–II and 11 grade III–IV toxicities, usually haematologic, digestive (nausea/vomiting, abdominal pain), and fatigue. Oxaliplatin concentrations were three- to four-fold higher in tissue in contact with aerosol than in muscle without contact. At 140 mg/m2, the plasma oxaliplatin concentration was high with Cmax and area under the curve (AUC)0–48h of 1035 μg/l and 9028 μg h/L, respectively. Conclusions The MTD of oxaliplatin during PIPAC is 90 mg/m2. PK data demonstrate a high tumour concentration and a significant systemic absorption.

Resume Objectif L’objectif de cette revue est de demontrer que la determination d’elements inorganiques ne figurant pas actuellement a la nomenclature des actes de biologie medicale (NABM), peut etre essentielle au diagnostic et a la prise en charge de patients presentant une carence ou une surcharge. Methodes Une recherche des recommandations concernant la determination d’elements inorganiques dans les matrices biologiques a ete effectuee aupres de differentes agences et organismes de sante publique et de societes savantes. Resultats Ces recommandations sont resumees dans cette revue pour les populations a risque du fait de conditions environnementales, nutritionnelles, metaboliques, genetiques ou en lien avec l’introduction de dispositifs medicaux implantables. Conclusion Afin d’eviter un retard dans le diagnostic ou une prise en charge inadaptee conduisant a une perte de chance pour le patient, nous estimons que plusieurs de ces dosages devraient etre integres rapidement a la NABM.

Summary For the last 10 years, recreational use of new psychoactive substances (NPS) with hallucinogenic properties was more and more described either in a context of consumption during a rave-party or at home alone or in small group. A review of 62 cases (56 M, 6 F, 16–46 y) registered from 2011 to 2016 at the French Grand Ouest centre antipoison of Angers is presented. Some of them (n = 15) presented a severe clinical state (poison severity score, PSS = 3) and only one was a fatal intoxication (PSS = 4). Treatment of acute intoxication was mainly based on supportive care with a quick recovery in less than 48 h. A high number of these cases were documented by plasma (pl) and/or urine analyses using LC-UV, GC-MS and LC-MS2. Several powders or other forms bought on the web market by the patients were also analysed. Six amphetamines derivates were detected such as methiopropamine (pl: 50 – 430 μg/L, n = 6) or 5 others (6-APB, 6-APDB, 5-EAPB, 5-MAPB, 2-FA each once). Four 2,5-dimethoxy-derivates of phenylethylamines (2Cs) or of amphetamines (DOs) were detected as 2C-P (pl

Summary Designer drugs appear to be increasing in popularity because of easy obtaining on the Internet, the lack of ability to identify the compound(s) in routine toxicology screening and being marketed as ‘legal’ substitute of drugs of abuse. 2,5-dimethoxy-4-chloroamphetamine (DOC) is a substituted alpha methylated phenethylamine and acts as a selective serotonin receptor partial agonist. There is limited literature on this particular compound, which is rarely encountered in biological matrices, and only one case-report attributed death to the use of this drug alone. We present five cases of non-fatal exposure to DOC with sever clinical symptoms (ages range 18–23 years). DOC was identified using data from LC/UV and GC/MS screening procedures. DOC in plasma and urine samples was quantified using a validated LC/MS/MS method and results showed that DOC plasma concentrations were less than 18 μg/L and DOC urine concentrations ranged from 300 to 1300 μg/L. This is the first documentation of DOC consumption in France, and in 4 cases, the patients believed that they were ingesting LSD. This indicates the emergence of designer drugs use as ‘legal’ LSD substitutes and we are concerned by the discrepancies in legal status of such compounds in the EU, which limit the effectiveness of drug enforcement policies.

Objectifs Le nombre d’intoxications pediatriques au cannabis apparait en constante augmentation depuis 2014 (ANSM, 19/10/2015). Ces intoxications touchent principalement les enfants de moins de 2 ans et font le plus souvent suite a l’ingestion accidentelle de residus cannabiques, presents dans l’environnement familial (ANSM, 19/10/2015). Cependant, bien que l’ingestion corresponde a la voie d’intoxication la plus frequente chez l’enfant, certains cas representent parfois une veritable gageure pour l’expert toxicologue. Ainsi, dans le contexte d’une expertise, il nous a ete demande de repondre a la question suivante : determiner si les concentrations de THC mise en evidence chez une enfant de 18 mois etait la consequence de l’ingestion d’un morceau de resine de cannabis ou liee a l’allaitement maternel (femme consommatrice reguliere). Methode Une fillette de 18 mois a ete controlee positive au cannabis. Trois prelevements (P) sanguins consecutifs (sur 17 heures) ont mis en evidence la presence de THC, de 11 OH-THC et de THC-COOH. Resultats P1 : THC : 37,5 μg/L, OH-THC : 28,0 μg/L ; THC-COOH : 235,0 μg/L ; P2 : THC : 44,0 μg/L, OH-THC : 37,2 μg/L, THC-COOH : 403,0 μg/L ; P3 : THC : 2,9 μg/L, OH-THC : 6,3 μg/L, THC-COOH : 219,0 μg/L. Conclusion Les modes d’exposition au cannabis chez les enfants de parents consommateurs apparaissent multiples et varies : inhalation passive de fumees de cannabis, ingestion de residus cannabiques, principalement. De plus, le THC est egalement retrouve dans le lait maternel ou il tend a se concentrer du fait de sa lipophilie. Chez des meres consommatrices regulieres, il est ainsi possible de retrouver, a des concentrations tres variables, du THC (1–323 μg/L), du 11-OH-THC (1,3–12,8 μg/L) et du cannabidiol (1,3–8,6 μg/L) (mais pas de THC-COOH ou de cannabinol) [1] . Les concentrations de THC decrites (1–323 μg/L) peuvent etre tres elevees (Centre de Reference sur les Agents Teratogenes, 06/03/2018 ; Drugs and lactation Database, 07/02/2019). Celles-ci dependent d’une part du delai ecoule entre le moment du prelevement et la derniere consommation de THC et d’autre part de la composition du lait maternel, variable d’une femme a l’autre. Ici, la mise en evidence de THC et de ses deux principaux metabolites, le 11 OH-THC et le THC-COOH, dans le sang, permet d’affirmer une consommation active : les concentrations sanguines de THC (ainsi que de 11 OH-THC et de THC-COOH) apparaissent en effet, en tant que telles, trop elevees pour pouvoir resulter d’une exposition passive, de nature environnementale [2] . Par ailleurs, les concentrations sanguines de 11 OH-THC sont du meme ordre de grandeur voire superieures aux concentrations sanguines de THC mesurees de facon synchrone, ce qui est tres en faveur d’une administration par voie orale de cannabis. Enfin, bien que l’ingestion de residus cannabiques demeure vraisemblable, l’hypothese que de telles concentrations soient la consequence de l’allaitement maternel ne peut etre formellement ecartee, dans la mesure ou dans les deux cas l’administration suit la voie orale et que la dose (ainsi que la biodisponibilite) de cannabinoides ingeree au cours de l’allaitement demeure largement inconnue. Ainsi, il apparait legitime de penser, eu egard aux donnees relatives a la pharmacocinetique du THC et aux cas rapportes dans la litterature [3] , que le « pattern » toxicologique observe dans les cas de l’allaitement maternel sera tres similaire a celui observe en cas d’ingestion de residus cannabiques. Dans ce contexte, la mesure des glucuronides serait peut-etre a meme d’apporter des elements (exposition chronique versus ponctuelle) permettant de discriminer les deux hypotheses.

Objectif Les nouvelles drogues de synthese dont les cathinones sont de plus en plus consommees pour leurs effets stimulants et entactogenes [1] . D’apres le rapport de l’OEDT publie en 2019, 138 cathinones ont ete repertoriees depuis 1997 en Europe. Des cathinones substituees, comme la N-ethylhexedrone (NEH), ont fait leur apparition depuis quelques annees. Nous decrivons le cas d’un homme ayant consomme a plusieurs reprises de la NEH sur 3 jours, son evolution clinico-biologique et sa prise en charge medicale. Methode Un homme de 39 ans avec des antecedents de syndrome depressif et de polytoxicomanie se presente aux urgences le mardi matin. Il dit avoir consomme du samedi au lundi matin de la NEH qui se presente sous la forme d’une poudre blanche cristalline. La dose totale supposee ingeree est de 1 g par voie sublinguale. Il se plaint d’une douleur buccale et linguale. L’examen clinique retrouve une anxiete, une agitation, un tremblement des extremites, une langue erythemateuse sans lesion ou œdeme. L’examen neurologique et cardiovasculaire est normal (TA 120/80 mmHg, FC 80–85/min, ECG normal). Aucune anomalie biologique n’est constatee. Le patient est simplement surveille pendant moins de 24 h et evolue favorablement en dehors d’une legere agitation psychomotrice persistante. Une recherche toxicologique large est effectuee sur tous les echantillons (sang, urine recueillie dans les 24 heures apres la derniere prise, reste de poudre) par LC-UV et par GC-MS avec ou sans derivation par HFBA. Des prelevements capillaires n’ont pas ete realises suite au refus du patient. Une methode quantitative a ete developpee par LC-MS/MS en mode ESI+ et MRM (220,2 > 202,0 ; 220,2 > 146,0). Apres precipitation des proteines avec du methanol (2/3, v/v) puis dilution ¼ dans l’eau, l’analyse chromatographique 2D (volume injecte : 10 μL) est effectuee par piegeage sur precolonne Strata-X (25 μm on-line extraction 20 × 2 mm) et separation sur colonne Kinetex Phenyl-Hexyl (2,6 μm, 100 × 3 mm). Le gradient d’elution est un melange 90/10 de formiate d’ammonium (2 mM)–0,2 % d’acide formique dans l’eau et dans l’acetonitrile, puis 65/35 en 8,5 min et 10-90 en 0,5 min. Resultats Les analyses ont confirme la presence de NEH et de metabolites dans les prelevements plasmatique (concentration inferieure a 10 ng/mL), urinaire (4810 ng/mL) ainsi que dans la poudre (purete de 60 %). Conclusion Kovacs et al. [2] rapportent des concentrations sanguines de NEH comprises entre 10,2 et 83,9 ng/mL (moyenne : 28,3 ng/mL, N = 1006 prelevements). En l’absence de donnee pharmacocinetique concernant la NEH, il est difficile d’extrapoler la dose ingeree par le patient. D’apres les sites d’utilisateurs, les doses generalement consommees sont comprises entre 5 et 50 mg, par voie intranasale ou orale ( www.psychonaute.org ). Les effets, apres une prise orale, debutent 20–25 minutes apres la prise et sont maximaux apres 1 h environ. Ils sont de differents types : sensation d’augmentation de l’energie physique, euphorie, acceleration de la pensee, augmentation de la motivation, de la concentration et de l’empathie, distorsion du temps, desinhibition.. Cependant, des effets adverses sont egalement possibles : deshydratation, hypersudation, vasoconstriction, augmentation de la frequence cardiaque et de la pression arterielle, bruxisme.. Lors de la phase de descente, il a ete decrit une persistance de la tachycardie et l’apparition d’un etat depressif, une anxiete, une irritabilite, une insomnie et une fatigue cognitive. Ce cas illustre les effets associes a la consommation cumulee importante de NEH sur 3 jours et leur persistance dans le temps.

Non-steroidal anti-inflammatory drugs (NSAIDs) are well known for their most frequent side effects (digestive, renal and metabolic disorders) but are lesser known for other effects, such as coagulation disturbances. In this issue, we report the case of a 58-year-old woman who ingested 26 g of naproxen in a suicidal attempt and developed cardiovascular shock, hypocoagulability and thrombopenia. Her outcome was positive (extubation 3 days after admission [D3], correction of haemostatic disruptions on D5 and of thrombopenia on D6). Naproxen plasma concentration was at a toxic concentration of 1320 mg/L at 6 hours after drug ingestion. Only few cases of hypocoagulopathy are reported with the NSAIDs, and this is the first case that can be attributed to naproxen. A possible explanation of this phenomenon following naproxen ingestion is an inhibition of thromboxane A2, usually attributed to NSAIDs, combined with an inhibition of activation of downstream the cascade.

International audience; Emerging evidence suggests that bariatric surgery improves pregnancy outcomes of women with obesity by reducing the rates of gestational diabetes, pregnancy-induced hypertension, and macrosomia. However, it is associated with an increased risk of a small-for-gestational-age fetus and prematurity. Based on the work of a multidisciplinary task force, we propose clinical practice recommendations for pregnancy management following bariatric surgery. They are derived from a comprehensive review of the literature, existing guidelines, and expert opinion covering the preferred type of surgery for women of childbearing age, timing between surgery and pregnancy, contraception, systematic nutritional support and management of nutritional deficiencies, screening and management of gestational diabetes, weight gain during pregnancy, gastric banding management, surgical emergencies, obstetrical management, and specific care in the postpartum period and for newborns.

Introduction: Voluntary drug intoxication with benzodiazepines is common and in most cases without consequences. We report an interesting case of voluntary drug intoxication with clobazam (CLB) in ...

A fixed-dose association of bismuth subcitrate, metronidazole and tetracycline (BMT) (Pylera®, Allergan, NJ, USA) was made available in France in 2013 for the eradication of Helicobacter pylori. Due to a historical issue of bismuth encephalopathy, the French Health Authorities requested a study of blood and plasma bismuth concentrations with BMT in daily practice. The aim of the study was to measure eventual bismuth accumulation and neurological toxicity in patients prescribed BMT. Patients initiating BMT for H. pylori between March 2014 and December 2015 were included. A blood sample was taken before first BMT intake and 24 h after the last intake, for assay of bismuth. A concentration > 50 μg/L was considered abnormal. Neurological complaints were assessed at inclusion, at the end of the 10-day treatment course, and 28 days later. 202 patients were included, of whom 190 took at least one dose of BMT, and 167 provided both required blood samples. Mean blood bismuth concentrations after the BMT course were 16.9 μg/L (95% confidence interval 15.6–18.3). Concentrations were > 50 μg/L (56.0 μg/L and 50.9 μg/L) in two elderly patients, one of whom presented mild, transient memory impairment during treatment. Non-serious neurological symptoms occurred in 20% of all patients and treatment failure was documented in 5% of patients. In this study measuring blood bismuth concentrations in real-life practice, in 50 μg/L. No serious neurological adverse events were observed. EU-PAS register EUPAS3142 at www.encepp.eu ; ENCePP study seal.

Resume Les AINS sont connus pour leurs effets indesirables les plus frequents (digestifs, renaux, metaboliques) mais d’autres le sont moins, comme les perturbations de la coagulation. Le cas d’une femme de 38 ans ayant ingere plusieurs medicaments dont le naproxene (dose supposee ingeree de 26 g) est rapporte. Elle est admise aux urgences avec un coma (Glasgow score de 4/15), necessitant une intubation endotracheale. Outre des troubles cardiaques (bradycardie sinusale), un allongement de l’espace QT a l’ECG, une acidose metabolique, elle presente une hypocoagulabilite et une thrombopenie a H7. Apres correction des troubles, elle est extubee a j3. L’analyse des prelevements d’admission a montre la presence d’acebutolol, de citalopram, d’oxazepam, de zopiclone et de naproxene (1320 mg/L). Les concentrations en naproxene diminuent sur les prelevements suivants avec une concentration de 250 mg/L a H47. Peu de cas d’hypocoagulopathie sont decrits avec les AINS, il s’agit du premier cas imputable au naproxene. Outre une inhibition des cyclo-oxygenases, des auteurs ont pose l’hypothese d’une action sur les facteurs de coagulation vitamine K dependants ou d’un mecanisme immunologique pouvant expliquer ce phenomene.

Resume Un cas medicolegal de decouverte de cadavre en lien avec une ingestion d’un herbicide, le dimethenamide-P, substance de la famille des chloroacetamides, est rapporte. Plusieurs approches analytiques sont mises en œuvre : CG-SM apres extraction sur microfibre (SPME) pour l’analyse de substances volatiles, CL-UV/BD et CG-SM apres extraction liquide-liquide pour la recherche large de toxiques et CL-SM/SM apres simple precipitation des proteines. L’analyse du liquide gastrique par SPME-CG-SM montre la presence de nombreux hydrocarbures aromatiques : isomeres de tetramethyl- et pentamethyl-benzene, naphtalene et ses derives mono- et dimethyles ou encore biphenyl-methyle, ces differents produits etant caracteristiques de naphta lourd. Le dimethenamide, identifie par son spectre de masse en CG-SM, est confirme par comparaison (spectre UV, MS et MS 2 ) avec la substance pure. La concentration, mesuree par CL-SM/SM 4 mois apres l’autopsie, dans le surnageant de centrifugation du sang cardiaque est egale a 10 mg/L pour l’echantillon conserve a −20 °C mais seulement egale a 1,3 mg/L pour le meme milieu conserve a +4 °C. La concentration dans le sang cardiaque conserve a +4 °C est egale a 0,66 mg/L. Les concentrations dans le liquide gastrique et dans la bile sont respectivement egales a 130 et 6 mg/L. En l’absence d’autre substance mise en evidence et d’autre cause formelle de deces, basee sur les donnees d’autopsie et d’anatomopathologie, la seule explication probable au deces est la presence du dimethenamide, le role du solvant naphta restant difficile a preciser. Aucun cas de deces ni d’intoxication par ce produit n’a ete retrouve dans la litterature.

Summary Alpha-methyltryptamine (AMT) is an analogue of endogenous tryptamine with psychotropic effects and is available on the web as designer drug or new psychoactive substance (NPS). A clinical case of a severe serotoninergic syndrome after ingestion of this substance is reported. The patient (male, 33 years), known as autist and poly-addict with a substitution treatment by methadone, was admitted at hospital (H0) for agitation. Tablets found in a bag at home should be methoxphenidine (MXP). Clinical symptoms suggested serotoninergic syndrome with Glasgow Score 10/15, diaphoresis, mydriasis, hyperthermia and tachycardia (140 beats/min). The major hyperthermia (42 °C) needed to transfer the patient in an intensive care unit (H4). The biological constants showed metabolic and respiratory acidosis with pH at 7.28, PaCO 2 6.5 kPa and lactates at 3.7 mmol/L. Creatinine was 156 μmol/L (325 on day D2), creatine phosphokinase (CPK) was 1973 U/L (26,895 on D2), ASAT and ALAT enzymes were at 75 N on D2 with prothrombin time

Background Therapeutic drug monitoring of carboplatin is based on its unbound clearance (CLU) determined by Bayesian analysis on unbound (U) concentrations. However, the ultrafiltration of plasma samples presents technical and time constraints. Therefore, this study aims to estimate CLU using total plasma (P) concentrations. Methods U and P concentration data of 407 patients were obtained from 2 clinical studies in which actual CLU had been determined for each patient. The patients were then split into development (277 patients) and prospective data sets (130 patients). Two approaches were evaluated. PK-model-only approach: a 3-compartment pharmacokinetic (PK) model based on U and P concentrations and taking into account the protein binding process was developed. The model with patient covariates was also evaluated. Linear regression approach: an equation (CLU = aCLP + b) was obtained by linear regression analysis between actual CLU and CLP, which is the total plasma clearance obtained by analyzing P concentrations according to a 2-compartment PK model. Predictive performance was then assessed within the prospective data set by estimating CLU from P concentrations using each approach and computing the relative percentage error (PE) between estimated CLU and actual CLU. Results The linear regression equation was CLU (L/h) = 1.15 CLP (L/h) + 0.13. The mean PE (MPE) between CLU (estimated using the equation) and the actual CLU was +1.2% (ranging from -31% to +33%) and the mean absolute PE (MAPE) was 9.7%. With the 3-compartment PK model, the MPE was +2.3% (ranging from -41% to +31%) and the MAPE was 11.1%. Inclusion of covariates in the 3-compartment model did not improve the estimation of CLU [MPE = +6.3% (from -33% to +37%); MAPE = 11.4%]. Conclusions The linear equation gives a relatively good estimation of CLU based on P concentrations, making PK-based carboplatin dose adaptation possible for centers without ultrafiltration facilities.

Objective Propofol is an intravenous anesthetic agent widely used in the induction and maintenance of general anesthesia. Acute intoxications with propofol are rare and remain primarily related to the acquisition of the product in hospital. If propofol can induce fatal respiratory depression alone, in a number of cases the clinical situation is exacerbated by the presence of other drugs like neuromuscular-blocking agents. Laudanosine, the circulating form of atracurium or cisatracurium, two non-depolarizing neuromuscular-blocking agents, is more frequently observed in toxicology. Such agents are widely used for tracheal intubations. Laudanosine has no pharmacological activity, which is exclusively due to the parent drugs. These agents can be fatal at any concentration, due to respiratory failure. Here, two cases of anesthesiologists’ suicide following self-administration of propofol-atracurium combination are reported. Case history Case 1: a 48-years-old anesthesiologist was found without vital signs at his office. The drugs and paraphernalia used for delivery were discovered at the scene. Case 2: a 61-years-old anesthesiologist was found dead at home with a cannula connected to an infusion set at the bend of the elbow. Next to the body several empty ampoules of Diprivan® and Atracurium besylate® were found. For both cases, several biological specimens were collected for toxicological investigation. Methods Comprehensive screenings of drugs and toxic compounds were performed using LC-DAD and GC-MS. Ethanol concentrations were determined using GC-FID. Laudanosine was quantified using LC-DAD. Propofol was quantified using GC-MS and LC-MS/MS. Results Propofol blood concentrations were 1 and 1.91 mg/L for case 1 and case 2, respectively (therapeutic range: 2–8 mg/L). Laudanosine blood concentrations were 0.13 and 1.18 mg/L for case 1 and case 2, respectively. Paroxetine, N-demethyldiazepam and ethanol were detected in the first case. Hydroxyzine was detected in the second case. In both cases, levels of these substances could not explain the death. Discussion Propofol related fatalities are rare, even more when combined with neuromuscular- blocking agents [1] . Propofol and atracurium concentrations documented here, are in agreement with those reported in the literature, these being characterized by a high inter-individual variability [2] . However, the concentrations observed in suicide cases compared to those observed in accidental fatalities (chronic abusers) appear to be much higher. In fact, three manners of death have been described with propofol: suicide, accidental overdose in chronic abusers, and more exceptionally, murder [3] . In the cases described here, circumstances and the use of atracurium suggest suicide. It should be noted that the concentrations of laudanosine and propofol observed here are in the usual anesthetic range. Albeit, it should be pointed out that for anesthetic agents, therapeutic concentrations are established for patients being supported respiratory-wise, while in non-supported or non-intubated patients such concentrations may be fatal. Therefore, the interpretation of the blood concentration in the forensic toxicological analysis must take into account the context and the circumstances of the death.

International audience; OBJECTIVE: We report two cases of elevated digoxin plasma levels in patients receiving enzalutamide. Cases reported: The first patient, an 84-year-old male treated with enzalutamide, was hospitalized due to deterioration in his general state. Atrial fibrillation was discovered and treatment with digoxin was initiated. Supratherapeutic digoxin concentrations (4 µg/L and 3.5 µg/L 3 days later) led to treatment being stopped despite the lack of clinical or biological signs of overdose. The second patient, an 84-year-old male treated with digoxin and enzalutamide, was hospitalized for the same reasons. Digoxin concentration upon admission was 2.8 μg/L. Despite stopping treatment, digoxin blood levels were observed to have increased on D3 and D7 following admission (3 and 3.6 μg/L, respectively). However, no clinical or biological findings indicated an overdose. Blood samples were sent to the Pharmacology and Toxicology Laboratory for analysis.METHODS: The second patient's digoxin plasma level was determined using the chemiluminescent microparticle immunoassay (CMIA®, Abbott, Illinois) method. Enzalutamide levels were determined using HPLC-UV/DAD method. An interference study was performed using different assay methods by adding enzalutamide to control plasma at various concentrations from a Xtandi (40mg) capsule.RESULTS: Plasma concentration of digoxin at D7 for patient 2 was identical in both laboratories (3.5 vs. 3.6 µg/L). Enzalutamide was found in the patient's plasma (12,5 mg/L). Adding 4, 10, 20, and 40 mg/L of enzalutamide to the untreated plasma showed that the plasma concentration of digoxin was positive (from 0.35 to 3.69 µg/L) using the CMIA method.CONCLUSIONS: Our results highlight the analytical interferences of enzalutamide with digoxin assays using the CMIA method.

International audience; Glioblastoma is the most frequent and aggressive primary malignant tumor of the central nervous system with a gloomy prognosis. Platinum derivatives and one among them, cisplatin, exhibited promising results when locally administered into the brain of glioblastoma bearing rats. Nanovectorization of anticancer agents through polymeric nanoparticles may even promote drug accumulation within cells, thus concentrating the drug efficiently at its target. Anchorage of gadolinium complexes on the corona of such smart drug delivery systems could further allow magnetic resonance imaging (MRI) monitoring of the nanoplat-form biodistribution in the damaged parenchyma and its therapeutic benefit. For this purpose, a biocom-patible amphiphilic triblock copolymer, made of degradable polyester and polycarbonate and bioelimin-able polyethylene oxide (PEO), was synthesized by successive ring-opening polymerizations. After micelli-zation in water, gadolinium complexes were grafted onto the PEO micelle corona and the carboxylate functions, located at the surface of the micelle's core, were able to cross-link with Pt(II) complexes. A macromolecular prodrug was therefore recovered in which more than one third of the carboxylate functions were linked to a platinum atom. By this strategy, stable cisplatin cross-linked nanoparticles were formulated with a mean size in the range of 100.63 ± 12.04 nm consistent with biological investigations. Relaxometry measurements both in water and in plasma at 7 T, 25 °C, confirmed the intrinsic potential of these hybrid nanoparticles as alternative MRI contrast agents with a substantial increase in the r 2 /r 1 ratio by a factor of 3.3 and 2.7, respectively, compared to the conventional low molar mass Gd-DTPA. As a result, their infusion within the striatum of glioblastoma-bearing mice resulted in a hypersignal on T 2-weighted MR images that persisted over time. Ultimately, the formulated prodrug exhibited up to 50-fold increased accumulation in human glioblastoma cell lines and up to 32-fold enhanced subsequent Pt-DNA adduct formation in comparison with free cisplatin, thus supporting the potential of this innovative bimodal tool for further applications.

Purpose: We aimed to evaluate the performance of therapeutic drug monitoring (TDM) approach in controlling interpatient variability of carboplatin exposure (AUC) in patients treated with TI-CE high-dose chemotherapy for advanced germ cell tumors and to assess the possibility of using a formula-based dosing method as a possible alternative. Experimental Design: Eighty-nine patients receiving carboplatin for 3 consecutive days during 3 cycles were evaluable for pharmacokinetic study. Blood samples were taken on day 1 to determine the carboplatin clearance using a Bayesian approach (NONMEM 7.2) and to adjust the dose on day 3 to reach the target AUC of 24 mg.min/mL over 3 days. On days 2 and 3, samples were taken for retrospective assessment of the actual AUC. A population pharmacokinetic analysis was also performed on 58 patients using NONMEM to develop a covariate equation for carboplatin clearance prediction adapted for future TI-CE patients, and its performance was prospectively evaluated on the other 29 patients along with different methods of carboplatin clearance prediction. Results: The mean actual AUC was 24.4 mg.min/mL per cycle (22.4 and 26.8 for 10th and 90th percentiles, respectively). The new covariate equation [CL (mL/min) = 130.7 × (Scr/83)−0.826 × (BW/76)+0.907 × (Age/36)−0.223 with Scr in μmol/L, BW in kilograms, age in years] allows unbiased and more accurate prediction of carboplatin clearance compared with other equations. Conclusions: TDM allows controlling and reaching the target AUC. Alternatively, the new equation of carboplatin clearance prediction, better adapted to these young male patients, could be used if TDM cannot be implemented. Clin Cancer Res; 23(23); 7171–9. ©2017 AACR.

Objective The consumption of new psychoactive substances (NPS), such as cathinones, has been on the rise over the last few years, with adverse effects ranging from agitation, anxiety and hallucinations to convulsions, severe cardiac, hepatic and renal failures [1] . This work aims to report and discuss a fatal case related to the concomitant use of two cathinone derivatives (CDs). Case history A 39-year-old man, known for drug addiction history, was found dead in his caravan. Multiple injection points were observed. The medical examiners concluded to a non-specific asphyxia syndrome combined with pulmonary and pericerebral edema and multivisceral congestion. Hence, the hypothesis of a death related to drug abuse was retained. Methods Blood and urine samples were collected for NPS identification and quantification using LC-HRMS. A metabolic study using human liver microsomes was also conducted to identify human metabolites compared to published studies in animals. Ethanol concentrations were determined using GC-FID and toxicological screenings were performed using LC-UVDAD, LC-MS/MS and GC-MS. Results Various analyses detected the presence of two CDs, 4′methyl-α-pyrrolidinohexanophenone (MPHP) and N-ethyl-4′methylnorpentedrone (4-MEAP), as well as tetrahydrocannabinol [(THC): 1.4 μg/L and (THC-COOH): 6.6 μg/L] and ethanol (0.5 g/L in cardiac blood). The concentrations of MPHP/4-MEAP in the femoral blood, cardiac blood and urine were 47/1.6, 97/3.5 and 2380/49,700 μg/L, respectively. The in vitro metabolic study allowed us to identify five metabolites for MPHP and three for 4-MEAP, but only two metabolites were detected at low levels in biological samples. One metabolite of MPHP, the 4′-carboxy-PHP, was detected in all biological samples, with higher chromatographic signals than those of MPHP. Conclusion Regarding the growing phenomenon of CD abuse, analytical toxicologists must have: – efficient tools to detect such NPS focusing on relevant biomarkers; – interpretation data (toxic and fatal blood levels) on CD. In this study, the CD concentrations found appeared to be of the same order of magnitude as the only two reports found in the literature, one concerning a case of death due to MPHP with a plasma (supernatant of heart blood) concentration of 32.9 μg/L [2] and another one on two cases of 4-MEAP intoxication with a positive outcome showing urine concentrations of 7676 and 4554 μg/L, respectively [3] . It is very likely that an additive or synergistic effect between both CDs might have precipitated the fatal outcome.

Objectif Une des principales difficultes rencontrees par les toxicologues analystes reside dans la veille scientifique et la mise a jour des bibliotheques des spectres de masse avec de nouveaux produits stupefiants, ou non. Nous presentons le cas d’une jeune femme ayant porte plainte pour viol et pour laquelle des analyses ont ete realisees dans trois laboratoires. Description du cas Lors d’une soiree, une jeune femme de 16 ans declare avoir bu quelques bieres, puis s’etre sentie mal, ne pouvant plus ni bouger, ni parler, tout en demeurant consciente. Le lendemain, soit environ 16 a 20 h plus tard, elle porte plainte et des prelevements sanguins et urinaires sont realises. Methode Dans un premier temps, apres extraction liquide/liquide en milieu alcalin, les prelevements sont analyses par LC-DAD. Les urines sont analysees par GC-MS sans et apres derivation avec du HFBA ou du BSTFA. Une recherche de psychotropes et benzodiazepines est egalement effectuee par LC-MS/MS dans les deux prelevements. Dans un second temps, l’echantillon urinaire a ete envoye au laboratoire d’Hombourg pour recherche de nouvelles drogues de synthese et drogues d’abus. Enfin, les echantillons ont ete adresses au CHRU de Lille ou des analyses par LC-HRMS ont ete realisees. Resultats Les analyses initiales ont mis en evidence un pic (temps de retention de 7,6 min) dans le sang et un pic additionnel a 6,0 min dans les urines. Les recherches de nouvelles drogues de synthese ou drogues d’abus sont negatives. Les dernieres analyses ont mis en evidence la presence de bilastine dans le sang peripherique (677 μg/L) et dans les urines (traces). Conclusion La bilastine est un nouvel anti-histaminique H1 non sedatif. Sa demi-vie est d’environ 15 h ; elle est peu metabolisee et son elimination est majoritairement urinaire. Les concentrations plasmatiques therapeutiques sont comprises entre 100 et 300 μg/L [1] . En cas de surdosage, les concentrations sanguines mesurees sont comprises entre 1 000 et 2 000 μg/L [2] . Les effets indesirables sont de type cephalees, somnolence, sensations vertigineuses et asthenie. L’absence de troubles de la conscience relates par la patiente ne semble pas en coherence avec une prise de bilastine ; il est cependant legitime de considerer que la concentration sanguine de bilastine pouvait etre compatible avec la survenue d’une somnolence. Dans tous les cas, sur le plan analytique, ce dossier illustre la necessite d’associer differents laboratoires et techniques d’analyse dans le but d’identifier de nouvelles substances. Il montre egalement l’importance de confronter les resultats analytiques aux donnees cliniques.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Spinal muscular atrophy (SMA) is a neuromuscular disorder of childhood. • Riluzole is an anti-excitatory agent recommended for the treatment of amyotrophic lateral sclerosis (ALS). • Riluzole pharmacokinetics are well documented in patients with ALS. WHAT THIS STUDY ADDS • Riluzole pharmacokinetics have never documented in patients with SMA. • This study showed that the administration of 50 mg riluzole once a day to patients with SMA leads to total riluzole daily exposure comparable with that obtained after the administration of 50 mg twice a day in healthy volunteers or ALS patients. AIMS The objective of the present study was to assess the pharmacokinetics of riluzole in patients with spinal muscular atrophy (SMA). METHODS Fourteen patients were enrolled in an open-label, nonrandomized and repeat-dose pharmacokinetic study. All participants were assigned to receive 50 mg riluzole orally for 5 days. Riluzole plasma concentrations were determined from samples obtained at day 5. RESULTS The pharmacokinetic analysis demonstrated that a dose of 50 mg once a day was sufficient to obtain a daily total exposure [AUC(0,24 h) = 2257 ng ml−1 h] which was comparable with results obtained in adult healthy volunteers or ALS patients in whom a dose of 50 mg twice a day is recommended. The pharmacokinetic simulation demonstrated that the administration of 50 mg twice a day could result in higher concentrations, hence reduced safety margin. CONCLUSION The dose of 50 mg once a day was chosen for the clinical trial evaluating the efficacy of riluzole in SMA patients.

BACKGROUND AND PURPOSE Treatment of organophosphate poisoning with pralidoxime needs to be improved. Here we have studied the pharmacokinetics of pralidoxime after its intramuscular injection alone or in combination with avizafone and atropine using an auto-injector device. EXPERIMENTAL APPROACH The study was conducted in an open, randomized, single-dose, two-way, cross-over design. At each period, each subject received either intramuscular injections of pralidoxime (700 mg), or two injections of the combination: pralidoxime (350 mg), atropine (2 mg), avizafone (20 mg). Pralidoxime concentrations were quantified using a validated LC/MS-MS method. Two approaches were used to analyse these data: (i) a non-compartmental approach; and (ii) a compartmental modelling approach. KEY RESULTS The injection of pralidoxime combination with atropine and avizafone provided a higher pralidoxime maximal concentration than that obtained after the injection of pralidoxime alone (out of bioequivalence range), while pralidoxime AUC values were equivalent. Pralidoxime concentrations reached their maximal value earlier after the injection of the combination. According to Akaike and to goodness of fit criteria, the best model describing the pharmacokinetics of pralidoxime was a two-compartment with a zero-order absorption model. When avizafone and atropine were injected with pralidoxime, the best model describing pralidoxime pharmacokinetics becomes a two-compartment with a first-order absorption model. CONCLUSIONS AND IMPLICATIONS The two approaches, non-compartmental and compartmental, showed that the administration of avizafone and atropine with pralidoxime results in a faster absorption into the general circulation and higher maximal concentrations, compared with the administration of pralidoxime alone.

Objectif Rapporter l’interet de l’apport analytique dans le diagnostic et la prise en charge d’une intoxication avec un insecticide organophosphore devant un tableau clinique peu contributif. Description du cas Une femme de 51 ans est hospitalisee apres ingestion volontaire d’un insecticide organophosphore (375 mL de chlorpyriphos methyl [CHLOM]) (Nuvagrain®), d’ethanol et de medicaments : tramadol, etodolac, diazepam et acide valproique. A sa prise en charge, l’aspiration gastrique permet de recuperer 250 mL d’un liquide pouvant correspondre au Nuvagrain®. Aux urgences, elle presente un score Glasgow de 10/15, une mydriase bilaterale reactive, des vomissements avec une hemodynamique stable (PA : 121/46 mmHg et FC : 71 bpm). Devant l’evolution clinique pejorative (hypotension (80/50 mmHg) et aggravation des troubles de la conscience), la patiente est intubee et transferee en reanimation. Un traitement antidotique par pralidoxime (Contrathion®) est debute. Un prelevement sanguin est effectue a l’admission, soit a H4 apres l’ingestion supposee. Le liquide preleve lors de l’aspiration gastrique et les urines n’ont pas pu etre recuperes pour analyse. L’evolution de l’etat de la patiente est favorable, avec une sortie a j7. Methode Les analyses biochimiques sont effectuees par des methodes (immuno)-enzymatiques (methode a la butyrylcholine pour les cholinesterases). Un premier screening toxicologique est realise au CHU d’Angers apres extraction liquide/liquide en milieu alcalin et analyse par LC-DAD. La presence de pesticides a ete egalement recherchee par UPLC-QTOF (G2-XS en mode ESI−) par le CHRU de Lille, apres precipitation du serum par du methanol. Resultats Le bilan montre une ethanolemie a 1,66 g/L, une ammoniemie a 105 μmol/L associee a une concentration en acide valproique a 135 mg/L. L’activite cholinesterase plasmatique est de 13 536 U/L (N : 4000–12 600 U/L). Le screening toxicologique montre la presence de midazolam et de citalopram ( Conclusion La presence d’ethanol et du CHLOM peut expliquer le tableau clinique de la patiente. Le dosage de la butyrylcholinesterase est moins bien correle aux effets toxiques que celui de l’acetylcholinesterase (AChE). De plus, aux faibles doses, les organophosphores inhibent surtout les AChE [1] . L’administration d’atropine n’a pas ete necessaire en raison de l’absence de syndrome muscarinique. Devant cette intoxication suspectee aux organophosphores, le pralidoxime a ete administre car son efficacite est optimale en cas d’administration precoce. Peu de cas d’intoxication au CHLOM sont decrits et documentes. Un seul cas de deces avec des concentrations de CHLOM dans le sang peripherique a 6,6 mg/L et de son metabolite a 42,9 mg/L a ete publie [2] .

International audience; Background:Dimethyl fumarate (DMFu) is a fungicide which is used in Chinese manufactures of furniture and shoes to avoid mould spoiling of fabrics. In 2008, DMFu was found the responsible allergen for several cases of contact dermatitis from armchairs and shoes observed in Europe. In France a national toxicovigilance survey was set up and importation of products containing dimethyl fumarate is now forbidden. Case report: a 36 year-old woman, with no history of previous allergy, was hospitalized because of a severe acute eczema of her feet after wearing a new pair of boots inside which she had noticed desiccant sachets. She strongly reacted on patch testing to DMFu and to the content of a sachet which was identified as DMFu, both at 0.01%, 0.1%, 1% in petrolatum, and also to a piece of the fabric of her boots, patch tested as is.Materials and method: Boot fabrics and mould-proof sachets found in the boots were analysed by HPLC/UV/DAD and GC/MS after methanol extraction. Further samples of anti mould agent sachets or shoe fabrics from 5 other patients with suspicion of DMFu dermatitis were analysed with the same procedure. Some of them were transferred to the laboratory several months after healing of the dermatitis.Results: DMFu was found in all the samples from 1 to 100% in sachets or from 20 to 2000 μg/g in the fabrics of shoes, even after one year. These findings contributed to ensure the responsibility of DMFu in the dermatitis of the patients and demonstrate that DMFu may remain a long time in the contaminated fabrics after removal of the sachets. This study also points out the usefulness of the collaboration between dermatologists, biologists and poison centre practitioners.

Introduction L’enzalutamide (Xtandi®), inhibiteur de la voie de signalisation des recepteurs aux androgenes, est un medicament indique dans le traitement du cancer metastatique de la prostate et commercialise depuis juin 2013. Nous rapportons ici 2 cas d’elevation de la digoxinemie chez des patients traites par enzalutamide. Cas rapportes Le 1er patient, un homme de 84 ans, traite habituellement par enzalutamide, est hospitalise pour une alteration de l’etat general. Une fibrillation auriculaire lente non connue est decouverte et un traitement par digoxine est instaure. Au cours de l’hospitalisation, une digoxinemie supratherapeutique (4 μg/L) conduit a la suspension du traitement. Le resultat du dosage de controle effectue 3 jours plus tard etant toujours tres eleve (3,5 μg/L), l’arret definitif de la digoxine est decide malgre l’absence de signe clinique ou paraclinique de surdosage. Le traitement par enzalutamide est egalement interrompu temporairement et le patient sort apres 43 jours d’hospitalisation. Le 2e patient, un homme de 84 ans habituellement traite par digoxine (125 μg/j) et enzalutamide (160 mg/j), est hospitalise pour alteration de son etat general. La concentration plasmatique de digoxine a l’admission est egale a 2,8 μg/L. Malgre l’arret immediat du traitement, une augmentation des digoxinemies est observee a j3 puis j7 (respectivement 3 et 3,6 μg/L). Cependant aucun element clinique ou paraclinique n’est cependant en faveur d’un surdosage : la kaliemie est normale (4,5 mmol/L), la fonction renale est normale (creatininemie 65 μmol/L), le patient est asymptomatique et l’ECG est inchange. L’hypothese d’une possible interference analytique lors du dosage plasmatique de la digoxine est donc evoquee par le CAPTV qui conseille un controle dans un 2e laboratoire. Methode La digoxine a ete dosee par immunochimiluminescence (CMIA®, Abbott) dans les 2 laboratoires. L’etude d’interference a ete faite par ajout d’enzalutamide sur un plasma temoin (EFS) a differentes concentrations (1, 10, 20, 40 mg/L) a partir d’une capsule molle de Xtandi® (40 mg) diluee dans 10 mL de methanol. La recherche d’enzalutamide dans le plasma du patient 2 a ete effectuee par CLHP-UV/BD. Resultats La digoxinemie a j7 pour le patient 2 est identique dans les deux laboratoires (3,5 vs 3,6 μg/L). L’enzalutamide est identifie dans le plasma du patient de meme qu’un autre produit de meme spectre UV correspondant tres vraisemblablement au metabolite N-demethyle. Les ajouts d’enzalutamide sur le plasma vierge montrent une positivite pour les concentrations 40, 20 et 10 mg/L avec des pseudo-digoxine respectivement egales a 2,73, 1,57 et 0,71 μg/L. La reponse est negative (

Objectif Decrire une intoxication peu frequente secondaire a un « sniff » de sel inorganique de mercure. Les expositions a ces sels sont bien connues, mais plutot par ingestion ou injection. Le tableau clinique peut etre dramatique avec des troubles digestifs hemorragiques, suivis d’un etat de choc et d’une anurie par necrose tubulaire [1] . Description du cas Dans un but suicidaire, un patient inhale la poudre d’un vieux flacon de « bichlorure de mercure ». A l’admission, il presente une irritation oropharyngee, un œdeme palpebral et des ulcerations de la cloison nasale, mais la fonction renale est normale. Des prelevements sanguins et urinaires ont ete effectues a son admission et quatre mois plus tard pour effectuer le dosage du mercure. L’evolution a ete favorable, le patient est reste asymptomatique par la suite jusqu’a la fin du suivi, 4 mois apres l’exposition. Methode Le dosage de mercure est effectue par ICP-MS (premier dosage effectue a l’hopital Lariboisiere et deuxieme au CHU d’Angers). Pour le deuxieme dosage, apres une pre-dilution avec du triton 0,2 %, l’echantillon est dilue avec une solution contenant 0,5 % d’acide nitrique et l’etalon interne (Rhenium). Resultats Lors du premier dosage, la concentration plasmatique du mercure etait de 1326,8 μg/L et sa concentration urinaire de 729,2 μg/g creatinine. Les concentrations mesurees dans les seconds prelevements etaient de 4,8 μg/L dans le sang et 23,9 μg/g creatinine dans l’urine. Dans la population generale, la concentration en mercure sanguin total est inferieure a 10 μg/L [3] et doit etre inferieure a 25 μg/L chez les personnes exposees professionnellement [2] (valeur fin de poste et fin de semaine). Dans le cas present, l’intoxication au mercure est confirmee par les dosages. Plusieurs arguments sont en faveur du bichlorure de mercure. Ce dernier est connu pour ses proprietes irritantes voire corrosives, mais egalement pour etre a l’origine de lesions renales. La concentration sanguine elevee peut probablement s’expliquer par une absorption importante par la muqueuse nasale [3] . Ce sel traverse difficilement la barriere hemato-encephalique, ce qui pourrait expliquer l’absence de signes neurologiques chez ce patient. Le patient a surtout presente des atteintes locales, mais pas d’atteinte viscerale. Par contre, en dehors de son activite de plombier-chauffagiste, il n’y avait pas d’information disponible sur une exposition professionnelle anterieure ou sur la consommation de poissons. Conclusion Il s’agit donc d’un cas original d’exposition nasale a un sel inorganique de mercure chez un patient qui a presente essentiellement des signes locaux sans atteinte viscerale, alors que les dosages sanguins et urinaires etaient eleves.

Objectif Presenter un cas de diabete insipide au cours d’une intoxication aigue par le baclofene et les benzodiazepines. Description Mme B., 43 ans, ethylique chronique en echec de sevrage et souffrant d’un syndrome depressif, est admise dans le service de reanimation medicale suite a la prise de 300 mg de baclofene et de benzodiazepines (quantite inconnue). La patiente presente un coma profond, avec un score de Glasgow a 3/15, et une abolition des reflexes du tronc cerebral. Un trace de burst suppression est retrouve a l’electroencephalogramme. A H6 de son admission en reanimation medicale, la biologie retrouve une hypo-osmolarite (94 mOsmol/L) et une faible densite urinaire (1000). La natremie est a 147 mmol/L, la creatinine est normale a 55 μmol/L. Une polyurie (3300 ml/6 h) y est associee. Un diabete insipide est donc evoque. Une hypotension persistante malgre un remplissage de 3 L au total necessite l’administration de noradrenaline. Des dosages de baclofene sont realises afin d’etablir une cinetique, ainsi qu’un screening toxicologique. Le baclofene a ete dose en LC-MS/MS apres precipitation des proteines. Les baclofenemies dosees sont presentees dans le Tableau 1 . Le screening retrouve du bromazepam a 0,42 mg/L et oxazepam a 4,50 mg/L. L’alcoolemie est a 0,22 g/L. Un peu plus de 24 h apres son admission, le reveil est calme et est associe a une resolution spontanee de son diabete insipide sans recours a la desmopressine, de facon concomitante a la decroissance rapide de la baclofenemie. La patiente est extubee par la suite. Discussion Les cas de diabete insipide au baclofene sont peu decrits dans la litterature. Il s’agirait tres probablement d’un mecanisme central car il repond bien a l’utilisation de desmopressine [1] . L’effet GABAergique du baclofene inhiberait les neurones producteurs d’ADH et cet effet pourrait etre potentialise par les benzodiazepines [2] . Cet effet ne semble etre rencontre qu’en surdosage et donc evoque un mecanisme dose-dependant. Conclusion L’implication du baclofene semble s’etablir dans la survenu d’un diabete insipide en cas de surdosage. Bien que rare, c’est un element a prendre en compte dans la prise en charge et la surveillance de patients intoxiques au baclofene afin de prevenir les complications qui peuvent y etre associees.

Objectif Le difenacoum est un anticoagulant anti-vitamine K, utilise comme raticide sous diverses formes. Ses parametres pharmacocinetiques dans l’organisme sont meconnus, a l’inverse de ceux du brodifacoum mieux documentes. L’objectif est de mieux definir les relations dose-effet-concentration du difenacoum dans un contexte d’intoxication per os. Methodes Une etude retrospective des cas d’intoxication par le difenacoum a ete realisee au centre antipoison (CAP) du CHU d’Angers sur tous les cas d’intoxication ayant fait l’objet d’une confirmation analytique. Cette analyse des cas d’ingestion notifies au CAP d’Angers a ete effectuee notamment sur la dose supposee ingeree, la surveillance clinico-biologique et les dosages plasmatiques de difenacoum realises par LC-DAD [1] . Resultats Cinq cas d’intoxication volontaire par difenacoum documentes par des analyses toxicologiques ont ete recenses par le CAP d’Angers. Ils concernaient 3 femmes et 2 hommes, âges de 33 a 82 ans. La concentration plasmatique maximale et le TP sont presentes dans le Tableau 1 . Conclusion La dose toxique du difenacoum n’est pas definie dans la litterature. A la vue des elements releves dans cette serie, il apparait que seuls quelques milligrammes de substances actives sont suffisants pour provoquer des troubles de la coagulation majeurs avec des repercussions cliniques hemorragiques significatives. Alors que la concentration plasmatique seuil du difenacoum, consideree comme toxique est estimee a 500 μg/L [2] , cette serie de cas indique que des effets sur la coagulation peuvent etre observes a des concentrations sanguines plus faibles. Les dosages plasmatiques des anticoagulants utilises comme raticide permettent de confirmer ces intoxications souvent volontaires et non avouees dans un contexte suicidaire ou criminel. La demi-vie est evaluee entre 7 et 45 jours [3] . Une surveillance clinico-biologique des patients est indispensable dans le cas de demi-vie prolongee. Dans de tels dossiers d’intoxication pouvant relever d’actes criminels, l’analyse capillaire pourrait participer a la mise en evidence d’eventuelles prises repetees.

Objectif Les cathinones, bien que classees comme stupefiants depuis juillet 2012, restent encore d’actualite. Cinq cas d’exposition impliquant 2 molecules encore peu decrites en France, l’ ?-pyrrolidinovalerophenone ( ?-PVP) et la 3-methyl-metcathinone (3-MMC) sont rapportes. Cas cliniques Les patients ont ete hospitalises apres consommation de nouvelles drogues de synthese (NDS) dans des cadres prives independants : 3-MMC ( n = 3), MDPV ou inconnue. Les symptomes sont essentiellement des hallucinations ( n = 3), agitation ( n = 3), tachycardie ( n = 3), hypertension arterielle ( n = 3) pour des Poison Severity Score (PSS) de 1 ou 2. Le traitement symptomatique a necessite une sedation dans 4 cas avec une evolution rapidement favorable. Des echantillons de sang et/ou urine et une poudre ont ete transmis pour analyses. Methodes Une recherche toxicologique large est effectuee par CLHP–UV/BD et par CG–SM avec ou sans derivation par HFBA. Une methode quantitative a ete developpee par CL–SM/SM en mode ESI+ et MRM pour les 2 molecules et l’oxo-PVP ( ?-PVP 232,2 > 90,9 ; 232,2 > 126,3 ; oxo-PVP 246,2 > 160,9 ; 246,2 > 91,1 ; 3-MMC 178,2 > 160,1 ; 178,2 > 145,0), apres precipitation des proteines par methanol (2/3 v/v) et dilution au ¼ dans l’eau suivie d’une chromatographie 2D (10 μL) avec piegeage « on-line » sur precolonne Strata-X (25 μm, 20 × 2 mm) et separation sur colonne Kinetex Phenyl-Hexyl (2,6 μm, 100 × 3 mm). Le solvant est un melange (90–10) de formiate NH 4 2 mM/acetonitrile avec chacun 0,2 % d’acide formique, puis 65–35 en 8,5 min et 10–90 en 0,5 min. Resultats L’analyse de la poudre par CLHP–UV/BD montre un produit ayant une analogie spectrale avec la pentedrone mais un Tr different. L’analyse par infusion en SM/SM oriente vers l’ ?-PVP, confirmee ulterieurement par comparaison a la substance de reference. La methode quantitative a ete validee, pour les 2 substances, entre 10 et 1000 μg/L. Les concentrations plasmatiques et urinaires sont presentees dans le Tableau 1 ci-dessous. Discussion Les 3 cas de MMC presentent des pics supplementaires correspondant vraisemblablement au metabolite N-demethyle et au metabolite dihydro sur la fonction cetone. Ce meme type de metabolite dihydro- est egalement suspecte pour les 2 cas de PVP. Pour le patient 1, un pic presentant un spectre UV comparable au 5-APB pourrait correspondre au 5-MAPB egalement suspecte. La symptomatologie de tous ces cas est peu specifique, et seule la determination analytique permet de confirmer ou d’infirmer les suspicions de prise de NDS.

Objectif Les nouvelles drogues de synthese (NDS) de type 2,5-dimethoxyamphetamine, egalement appelees DOx, sont des homologues chimiques des phenylethylamines de la serie 2C, avec differentes substitutions en position 4 du noyau phenyle. Elles possedent des proprietes hallucinogenes. Cinq cas d’hospitalisation suite a une consommation de DOC (2,5-dimethoxy-4-chloro-amphetamine) sont presentes. Cas cliniques Cinq hommes âges de 16 a 23 ans ont ete hospitalises apres consommation de NDS dans un cadre prive ( n = 2) ou de Rave-party ( n = 3). Dans 4 cas (Poison Severity Score [PPS] 2), les patients disent avoir consomme des buvards de LSD. Les symptomes sont essentiellement psychiatriques, avec des hallucinations jusqu’a 24 h apres prise, une agitation et une angoisse. Quatre d’entre eux presentent une mydriase et 2 ont une tachycardie jusqu’a 150/min. Un patient (PSS 3) presente des convulsions. Le traitement est symptomatique avec une evolution rapidement favorable. Des prelevements sanguins et urinaires ainsi qu’une poudre sont transmis au laboratoire. Methodes Une recherche toxicologique large est effectuee sur tous les echantillons par CL-UV/BD et par CG-SM avec ou sans derivation par HFBA. Une methode quantitative a ete developpee par CLHP-SM/SM en mode ESI+ et MRM pour 8 DOx dont la DOC (230,1 > 213,0 ; 230,1 > 185,0) pour le plasma et l’urine (apres dilution dans un plasma vierge). Apres precipitation des proteines par methanol (2/3 v/v) puis dilution ¼ dans l’eau, l’analyse chromatographique 2D (inj. 10 μL) est effectuee par piegeage sur precolonne Strata-X (25 μm on-line extraction 20 × 2 mm) et separation sur colonne Kinetex Phenyl-Hexyl (2,6 μm, 100 × 3 mm). Le gradient d’elution est un melange 90-10 de formiate NH 4 (2 mM) et d’acetonitrile avec chacun 0,2 % d’acide formique, puis 65/35 en 8,5 min et 10-90 en 0,5 min. Resultats Toutes les urines presentent un meme pic chromatographique, ayant une analogie spectrale UV forte avec le 2C-C mais un Tr different. L’analyse de la poudre a montre la presence de la meme substance permettant ensuite d’affirmer qu’il s’agissait de DOC. La methode quantitative a ete validee entre 10 et 1000 μg/L. Les concentrations plasmatiques et urinaires sont presentees dans le Tableau 1 . Conclusion La DOC, agoniste partiel des recepteurs serotoninergiques, n’est pas detectee par les tests d’immunoanalyse de type amphetamine. Or la DOC, substance licite, s’avere etre un substitut possible du LSD avec des symptomes psychiatriques, neurologiques et cardiovasculaires pouvant etre importants. Les molecules de la classe des DOx ne doivent donc pas etre oubliees face a de tels symptomes pour assurer une prise en charge optimale des patients.

International audience; BACKGROUND: Although zinc deficiency is common after bariatric surgery, its incidence is underestimated. The objective was to monitor zinc and nutritional status before and 6, 12 and 24 months (M6, M12 and M24) after gastric bypass (Roux-en-Y gastric bypass), sleeve gastrectomy and biliopancreatic diversion with duodenal switch (DS) in patients receiving systematised nutritional care.METHODS: Data for 324 morbidly obese patients (mean body mass index 46.2 ± 7.3 kg/m(2)) were reviewed retrospectively. The follow-up period was 6 months for 272 patients, 12 months for 175, and 24 months for 70. Anthropometric, dietary and serum albumin, prealbumin, zinc, iron and transferrin saturation measures were determined at each timepoint.RESULTS: Nine percent of patients had zinc deficiency pre-operatively. Zinc deficiency was present in 42.5% of the population at M12 and then remained stable. Zinc deficiency was significantly more frequent after DS, with a prevalence of 91.7% at M12. Between M0 and M6, variation in plasma prealbumin, surgery type and zinc supplementation explained 27.2% of the variance in plasma zinc concentration. Surgery type explained 22.1% of this variance between M0 and M24. Mean supplemental zinc intake was low (22 mg/day). The percentage of patients taking zinc supplementation at M6, M12 and M24 was 8.9%, 20.6% and 29%, respectively.CONCLUSIONS: Reduced protein intake, impaired zinc absorption and worsening compensatory mechanisms contribute to zinc deficiency. The mechanisms involved differ according to the type of surgery and time since surgery. Zinc supplementation is necessary early after bariatric surgery, but this requirement is often underestimated or is inadequate.

International audience; Background: Immunochromatographic drug tests are more and more involved in the initial biological survey of acute poisoning, even with “on site” use at the emergency unit. Specificity of the drug-antibody interaction is both an advantage (rapid, easy-to-perform tests, no apparatus) and a limitation (cross-reactivity, interferences).Patient cases: A 13-year-old girl was admitted at an emergency unit for somnolence and respiratory acidosis. A multi8 rapid drug test was positive for benzodiazepines, methadone (MTD) and phencyclidine (PCP). To avoid false diagnosis, fluorescence polarization immunoassay, liquid- and gas-chromatography were also performed on both plasma and urine. Rapid tests (different batches) from the same and other manufacturers were involved for this patient and other therapeutic, acute or forensic cases.Results:Bromazepam was identified in plasma (0.4 mg/L) and urine but also tramadol (respectively 0.5 and 25 mg/L), its metabolites and, in urine only, norpropoxyphene (NPPX). No methadone was detected. Among 7 other cases with tramadol detected in urine, 5 were positive with PCP test and 5 with MTD. Drug-added urines confirmed false-positive results for PCP with tramadol but for MTD with NPPX. While tramadol cross-reactivity is very low (0.05%), positive tests, even in a therapeutic context, were observed because phencyclidine cut-off is only 25μg/L. Tramadol can also positive MTD test at very high urine level. The NPPX cross-reactivity, initially 100%, was theoretically reduced to less than 0.025% after a modification of antibody by the manufacturer. Structurally-related formulas could explain such positive results but tests from other manufacturers were negative except in one case with tramadol.Conclusion: The analytical performances (sensitivity, specificity) of such rapid tests must be known by clinicians to avoid false-positive diagnosis. The “on site” use at the emergency unit must be considered as a preliminary test that should be confirmed by alternative methods in a laboratory area. Data exchange between biologists, clinicians and manufacturers is needed to improve the quality of results.

International audience; Allergic diseases are characterized by the activation of inflammatory cells and by a massive release of mediators. The aim of this chapter was to describe succinctly the modes of action, indications, and side effects of the major antiallergic and antiasthmatic drugs. When considering the ideal pharmacokinetic characteristics of a drug, a poorly metabolized drug may confer a lower variability in plasma concentrations and metabolism-based drug interactions, although poorly metabolized drugs may be prone to transporter-based disposition and interactions. The ideal pharmacological properties of a drug include high binding affinity, high selectivity, and appropriate association and dissociation rates. Finally, from a patient perspective, the frequency and route of administration are important considerations for ease of use.