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In recent years, a class of new designer drugs commercialized under the generic name of “Synthacaines” have been available both to the surfaceweb and the illicit drug market or deep web. We report the case of a 30-year-old man admitted to the psychiatry department for acute anxiety crisis with paranoid experiences associated with dysmorphophobia, who followed one week of intensive use of “synthacaine” he bought on the web. Toxicological analysis of the powder consumed by the patient allowed to identifying a mixture of 4 different drugs: 2-aminoindane, N-methyl-2-amino-indane, methiopropamine and lidocaine.

Objectives Assess the stability of several antibiotics in peritoneal dialysis (PD) solutions under common conditions of use in pediatrics, particularly in automated PD.Methods Amoxicillin, cefazolin, cefepime, ceftazidime, imipenem, cotrimoxazole, tobramycin, vancomycin, and the association of ceftazidime + vancomycin and ceftazidime + tobramycin, were tested in 3 different PD solutions: bicarbonate/lactate solution with 2 glucose concentrations (Physioneal 1.36 and 3.86%; Baxter Healthcare Corporation, Deerfield, IL, USA) and an icodextrin-containing solution (Extraneal; Baxter Healthcare Corporation, Deerfield, IL, USA). Concentrations were those recommended in guidelines for the treatment of peritonitis in pediatrics. Physioneal bags were incubated at 37°C for 24 hours, whereas Extraneal bags were stored 12 hours at room temperature (22 ± 2°C) and then 12 hours at 37°C. Drug concentrations were determined using high performance liquid chromatography (HPLC). Each measure was taken in triplicate. Stability of antibiotics was defined as less than 10% degradation of the drug over time.Results Cefazolin, cotrimoxazole, tobramycin, and vancomycin were stable under studied conditions. Ceftazidime was stable 24 hours in icodextrin, 12 hours in Physioneal 1.36% and 6 hours in Physioneal 3.86%. The association of tobramycin or vancomycin did not influence the stability of ceftazidime. Cefepime and amoxicillin were stable 6 h, 4 h, and 8 h in Physioneal 1.36%, 3.86% and Extraneal, respectively. The stability of imipenem was very low: 2 h in Physioneal and 6 h in Extraneal. Moreover, an increasingly yellow coloration was observed with the use of imipenem, whereas no color change or precipitation occurred in other bags.Conclusion Cefazolin, tobramycin, cotrimoxazole, and vancomycin are stable in PD solutions up to 24 hours and can be administered in the PD bag for the treatment of peritonitis, even in automated PD under studied conditions. However, amoxicillin, cefepime, ceftazidime, and imipenem must be used with caution due to their lack of stability.

Brimonidine is a selective alpha-2-adrenergic agonist used to treat glaucoma. We report a case of a 9-day-old female who developed, 90minutes after accidental ingestion of 3 eye drops of 0.2% brimonidine, coma, apnea, hyperglycemia and miosis requiring intubation and mechanical ventilation. Plasma concentration, 3hours after intake, was 11.7ng/mL. Normal consciousness was reached after 27hours. Apnea recovered slowly, normal breath was reached 47hours after accidental intake. This report adds to the existing evidence that brimonidine has serious systemic effects in newborns and can require fast and supportive management in intensive care unit.

L’intoxication massive au paracétamol peut se compliquer d’une acidose lactique précoce sans anomalie du bilan hépatique. Nous présentons le cas d’un homme de 60ans, hospitalisé pour une intoxication médicamenteuse volontaire massive de 64g (soit 914mg/kg). Pendant les 3jours d’hospitalisation, ont été suivis en parallèle : la concentration plasmatique en paracétamol, en lactates, en ASAT et ALAT ainsi que le taux de prothrombine. Le bilan d’entrée aux urgences médicales révèle une paracétamolémie à 720mg/L (4766μmol/L), une acidose lactique décompensée (lactates : 10,2mmol/L ; pH : 7,27 ; trou anionique : 24mmol/L) et un bilan hépatique normal. Le traitement par N-acétyl-cystéine en perfusion intraveineuse est débuté avec une dose de charge de 150mg/kg en 1heure suivie de 50mg/kg en 4heures puis 100mg/kg en 16heures. Il est ensuite transféré en réanimation médicale dans un coma agité. L’acidose lactique se corrige en 12heures avec une cinétique des lactates superposable à celle du paracétamol. Du fait d’une paracétamolémie encore élevée 20heures après l’ingestion (1218μmol/L), le traitement par N-acétyl-cystéine est continué sur une base de 100mg/kg/24h. La paracétamolémie est infra-thérapeutique (inférieure à 33μmol/L) 44heures après l’ingestion. L’absence d’état de choc concomitant, d’état d’hypoxie ou de convulsions, de prise médicamenteuse autre, d’arguments en faveur d’une intoxication au monoxyde de carbone ainsi que d’une fonction hépatocellulaire normale permettent d’étayer l’hypothèse physiopathologique de l’intoxication massive au paracétamol. Ce type de cas, bien que très rare, doit être connu des cliniciens réanimateurs.

Substitution of a non-nucleoside reverse transcriptase inhibitor (NNRTI) with another drug of the same class combined with nucleoside reverse transcriptase inhibitors is a therapeutic strategy that can improve the tolerability of antiretroviral treatment. According to the pharmacokinetic properties of NNRTIs, this substitution generates pharmacokinetic drug interactions between NNRTIs, which could decrease NNRTI exposure and virological efficacy during the introductory phase of the new NNRTI. Pharmacokinetics and clinical data are reviewed to estimate the risk for switching from efavirenz to nevirapine, efavirenz to etravirine, efavirenz to rilpivirine and nevirapine to rilpivirine.

L’oxycodone est un morphinique de plus en plus prescrit dans la prise en charge de douleurs aigues et chroniques. Nous décrivons un cas mortel d’intoxication aiguë volontaire à l’oxycodone chez un patient souffrant d’un syndrome douloureux chronique.

Présenter un cas d’administration de médicaments par un tiers chez un enfant hospitalisé pour maltraitance.

High-dose methotrexate remains a mainstay in the treatment of acute lymphoblastic leukaemia, osteosarcoma and non-Hodgkin lymphoma. Therapeutic drug monitoring of plasma MTX is important to monitor efficacy and adverse events. The authors aimed at developing a liquid chromatography tandem mass spectrometry (LC-MS/MS) method with online extraction to determine MTX and 7-OH-MTX in plasma for therapeutic drug monitoring. The analysis combined straightforward sample preparation, consisting of protein precipitation with methanol/ZnSO4, with a 4-minute run time consisting of an on-line enrichment by a flush/back-flush cycle (Poros column, R1/20, 2.1 mm × 30 mm) before the second dimension chromatography (Phenomenex Luna 5 μm Phenyl Hexyl, 2 mm × 50 mm column). Samples were analysed using an HPLC Agilent 1200 Series and ABSciex API 3200. The electrospray was operated in positive ionization mode monitoring the following mass transitions: m/z455.11 → 308.3 for MTX, 471.14 → 324.3 for 7-OH-MTX and m/z459.1 → 312.3 for internal standard (MTX13C2H3). The method was linear up to 50 μmol L−1, and intra-day and inter-day quality control CVs were below 8.3% for MTX and 11.71% for 7-OH-MTX. Average recovery was 24% for MTX and 57% for 7-OH-MTX. The lower limit of quantitation was 25 nmol L−1for the 2 analytes. For MTX and 7-OH-MTX the standard line slope CV percentage was <3% and the slope difference <6%, indicating that our analytical method is almost free from a significant relative matrix effect. Method comparison with the Abbott TDx fluorescent polarization immunoassay (FPIA) showed excellent agreement: LC-MS/MS = 0.0011 + 1.0334 (FPIA). Because of antibody cross-reactivity between DAMPA and MTX, none of the immunoassays can be used after carboxypeptidase administration. The goal of our work was to develop a specific LC-MS/MS method to monitor both MTX and 7-OH-MTX plasma concentrations within the clinically relevant range. It's expected that the LC-MS/MS method for MTX monitoring after carboxypeptidase administration will be very rarely used since it concerns only exceptional cases. Therefore, the geographically balanced distribution of University Hospital able to ensure follow-up of these patients, within 24 hours of collection, can draw a reliable solution for the security of the patients. We develop a fast and reliable LC-MS/MS method for both routine TDM of MTX as in the setting of carboxypeptidase therapy.

Numerous laboratories carried out simultaneous whole blood quantitation of everolimus, sirolimus, tacrolimus and cyclosporine-A on a liquid chromatography-tandem mass-spectrometry (LC-MS/MS) system with online solid phase extraction (SPE) after manual deproteinization and centrifugation. This method had a relatively low sample throughput due to labor intensive and time-consuming sample preparation. We develop a fast and robust method of semi-automated whole blood sample pre-treatment able to support over 120 samples daily. Whole blood samples were mixed in a V-bottom plate with 2 volumes of ZnSO4/methanol containing deuterated internal standards. After centrifugation, the supernatant was loaded on an online-SPE before being transferred and monitored on the LC-MS/MS system. Assay performance included inter- and intra-day accuracy and imprecision, relative and absolute matrix effects, extraction recovery and selectivity. Intra- and inter-day imprecision was <15% for all tested concentrations. The lower limit of quantification of cyclosporine-A, everolimus, sirolimus and tacrolimus was respectively 26.6, 1.13, 1.57 and 1.28 ng mL−1, with an accuracy between −0.63% and 11.48% and a precision <12% of the nominal concentration. Standard line slope imprecision did not exceed 20% and ion enhancement or suppression was negligible. The comparison methods were performed by Passing and Bablok regression analysis: a high correlation was found between the two pre-treatment methods for tacrolimus, everolimus and sirolimus and between LC-MS/MS vs.radio-immuno-assay for cyclosporine-A. We developed a fast, sound and less misleading analytical method for high throughput (over 120 samples daily) therapeutic drug monitoring of multiple immunosuppressive drugs in routine practice.

La ceftriaxone est une céphalosporine de 3egénération possédant une pharmacocinétique originale, caractérisée par une demi-vie d’élimination longue par rapport aux autres céphalosporines, une liaison protéique importante et une élimination mixte rénale et biliaire. Il en résulte une variabilité importante des paramètres pharmacocinétiques dans des situations cliniques telles que l’insuffisance rénale sévère, l’insuffisance rénale et hépatique associée, les sujets âgés, les nouveau-nés (<1 semaine) et chez les patients en soins intensifs. Dans ces situations cliniques et/ou dans les infections où le germe impliqué possède une concentration minimale inhibitrice (CMI) élevée, l’existence d’une relation concentrationefficacité basée sur le rapport concentration plasmatique résiduelle sur la CMI peut permettre d’adapter la posologie de la ceftriaxone. Le suivi thérapeutique pharmacologique (STP) est classé comme éventuellement utile dans ces situations. En matière de toxicité, l’intérêt du STP de la ceftriaxone reste à démontrer.

L’hydroxychloroquine est un médicament prescrit dans le traitement de la polyarthrite rhumatoïde et du lupus érythémateux disséminé (LED). Dans cette étude, nous décrivons une interférence analytique de l’hydroxychloroquine lors de la recherche automatisée de la buprénorphine dans l’urine (méthode CEDIA®, Thermo Scientific®, sur COBAS 8000 c502 Roche Diagnostic®), ayant conduit à un résultat faussement positif chez une patiente.

Le fentanyl est un analgésique opioïde de palier 3, commercialisé en France sous forme injectable et transdermique, prescrit dans la prise en charge des douleurs aigues et chroniques. Nous décrivons deux cas d’intoxication aiguë mortelle dans un contexte de mésusage du fentanyl.

We report a case of colchicine-induced rhabdomyolysis in a heart/lung-transplanted man treated with cyclosporin. A treatment was to resolve an acute gouty arthritis and was started with 3 mg of colchicine the first day, then 2 mg the second and the third day, and finally 1 mg/d during 6 days. Eight days later, the patient developed multiple organ failure and rhabdomyolysis. The concentration of colchicine analyzed was greater than the standard 153 hours after his last intake. Pharmacokinetic interactions are responsible of this toxicity. Cyclosporin, pravastatin, and azithromycin are known to inhibit P-glycoprotein, which will enhance the intracellular colchicine level by acting in its bioavailability and moderating hepatic and renal excretion. Moreover, long-term treatment by cyclosporin generates chronic renal failure that will, in the same time, decrease colchicine elimination. Even short-term administration of therapeutic colchicine dose may cause colchicine-related toxicity, especially in the setting of a renal failure and/or polymedicinal treatment.

Optimal dosing of continuous-infusion cefazolin can be challenging in patients being treated for bacteremia or infective endocarditis. The aim of this work is to describe and analyze the pharmacokinetics of cefazolin in those patients using a population pharmacokinetics modeling approach and to establish a nomogram to determine the optimal daily dose. Population pharmacokinetics were modeled using the Pmetrics package for R.

High dosages of ceftriaxone are used to treat central nervous system (CNS) infections. Dosage adaptation according to the glomerular filtration rate is currently not recommended. Ceftriaxone pharmacokinetics (PK) was investigated by a population approach in patients enrolled in a French multicenter prospective cohort study who received high-dose ceftriaxone for CNS infection as recommended by French guidelines (75 to 100 mg/kg of body weight/day without an upper limit).

A patient received continuous infusion of cefazolin 10 g then 8 g daily for an external ventricular drainage-related methicillin-susceptible Staphylococcus aureus(MSSA) ventriculitis. Median free concentrations in the cerebrospinal fluid were 11.9 and 6.1 mg/liter after 10- and 8-g doses, respectively.

ABSTRACTAn obese woman was treated with oral tedizolid 200 mg once daily for pseudoarthrosis 10 years after Roux-en-Y bypass surgery. Total plasma peak concentration was 2.12 mg/liter 3 h after intake, and area under the concentration-time curve from 0 to 24 h (AUC0–24) was 28.3 mg/liter · h. The AUC0–24/MIC ratio for unbound concentrations and for sensitive Staphylococcusand Streptococcusstrains was ≥10.8, higher than the target ratio of 3. These results support the use of tedizolid without adjustment after bariatric surgery.

ABSTRACTPosaconazole is an antifungal drug used in both prophylaxis and treatment of invasive fungal infections. Its oral formulation requires therapeutic drug monitoring. To overcome gastric acidity, a gastro-resistant posaconazole tablet has recently been developed. POSANANTES was a prospective noninterventional study that aimed to monitor plasma concentration trough level (Cmin) of posaconazole tablets used prophylactically in patients with hematological malignancies. Fifty patients were included. Group A (n= 31) included patients receiving induction chemotherapy for myeloid malignancies, and group B (n= 19) included patients treated for graft-versus-host disease after allogeneic hematopoietic stem cells transplantation. In multivariate analysis, female sex, group B assignment, and evaluation of Cminat day 8 (versus any other day planned by the analysis) were associated with a higher Cmin, while diarrhea was associated with a lower Cmin(P< 0.05). Thirty-four percent (n= 17) of all included patients had to prematurely stop treatment, mainly in group A. In conclusion, this real-life prospective study showed good absorption of posaconazole tablets used for prophylaxis in patients with hematological malignancies, even though this strategy was somewhat limited due to the high number of patients in group A who had to stop their treatment in an untimely fashion.

L’usage et l’abus de substances psychoactives dans un contexte sexuel (ChemSex) et le SLAM (injection en intraveineuse de ces substances) sont des phénomènes émergents dans le milieu gay pouvant avoir de graves conséquences. La 4-MEC (4-méthylethcathinone) est une cathinone de synthèse, famille de substances fréquemment associée à ces pratiques.