Suivi thérapeutique pharmacologique (STP) et principes pharmacocinétiques : application aux Immunosuppresseurs

Date du colloque&nbsp;: 04/2008</p

Tests immunochromatographiques : faux positifs à la méthadone et à la phencyclidine en relation avec une intoxication par tramadol et dextropropoxyphène

Date du colloque&nbsp;: 10/2009</p

Pharmacokinetics of secnidazole in healthy volunteers after single oral dose

Introduction: Secnidazole is an anti infective agent which belongs to the 5-nitroimidazole class. Method: The objective of the trial was to characterize the pharmacokinetics of secnidazole after oral administration of a 2g dose, as microgranules formulation in healthy subjects. Blood samples were collected before, 1, 2, 3, 6, 9, 12, 24, 36, 48, 72, 96, 120, 168 and 240 h after dosing. Urines were collected in 24-h-fractions for the first five days and in 48 h-fraction for the last sample. The cumulative urinary excretion was captured for each subject from urine concentration (lg/L). Pharmacokinetic parameters were obtained by a non-compartmental approach (WinNonlin Pharsight). The assay was performed by ultra-performance liquid chromatography coupled with mass spectrometry detection (UPLC-MS/MS, Quattro Premier, Waters) after simple protein precipitation of 50 lL plasma sample. Chromatographic separation was done on a C18 Acquity column (50 mm · 2.1 mm, id 1.7 lm, Waters), in isocratic mode (80% water/0.1% formic acid and 20% acetonitrile). Ornidazole was used as internal standard. The detection was operated in positive mode and multiple reaction monitoring was used for quantification (186 &gt; 128 ion transition for secnidazole). The lower limit of quantification was 10 and 100 lg/L for plasma and urine samples respectively. Results: Sixteen subjects (8 female, 8 male) were included. Population characteristics such as: age ranged from 23 to 50 years (mean ± SD: 38 ± 9.2 years), weight ranged from 51 to 90 Kg (mean ± SD = 64.6 ± 10.1 Kg) and body mass index (BMI) ranged from 19.9 to 24.2 Kg/m 2 (mean ± SD = 21.9 ± 1.5 Kg/m 2 ;). Secnidazole exposure achieved a maximal concentration (Cmax) with a mean of 37.9 ± 8.5 mg/L (range 20–56 mg/L) and at a median time associated with the Cmax (Tmax) of 6 h (range 3–6 h). The area under the curve to the last measurable time (AUC0_t) and the total area under the curve (AUC0_¥) were 1281.9 ± 416.4 mg h/L and 1304.2 ± 444.1 mg h/L (mean ± SD) respectively. The Cl/F and V/F were 1.7 ± 0.5 L/h and 40.2 ± 9.2 L respectively and the elimination half-life (t1/2) was 17.5 ± 4.3 h (mean ± SD). The mean amount of secnidazole excreted in the 168-h urine collection was 310.47 mg (15.5% of the administered dose). For example, for the subject number 5, the observed parameters are: Cmax 37.3 mg/L, Tmax 3 h, AUC0_¥ 1029.5 mg h/L and t1/2 15.6 h. Conclusion: After a 2 g single oral dose, secnidazole presents a good absorption profile and relatively long elimination half life ensuring probable sufficient exposure with once a day administration

Dosage de la metformine par chromatographie liquide en mode Hilic couplée à la spectrométrie de masse en tandem: application à 5 cas d&#039;acidose lactique

National audienc

Intoxications aiguës par le pentobarbital: un vieux produit toujours d&#039;actualité

National audienc

Contribution of toxicological analysis to the care of dimethyl fumarate dermatitis

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

High-performance liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS) method for the simultaneous determination of diazepam, atropine and pralidoxime in human plasma

A high-performance liquid chromatography coupled with electrospray tandem mass spectrometry (LC/MS/MS) procedure for the simultaneous determination of diazepam from avizafone, atropine and pralidoxime in human plasma is described. Sample pretreatment consisted of protein precipitation from 100 μl of plasma using acetonitrile containing the internal standard (diazepam D5). Chromatographic separation was performed on a X-Terra® MS C8 column (100 mm × 2.1 mm, i.d. 3.5 μm), with a quick stepwise gradient using a formate buffer (pH 3, 2 mM) and acetonitrile at a flow rate of 0.2 ml/min. The triple quadrupole mass spectrometer was operated in positive ion mode and multiple reaction monitoring was used for drug quantification. The method was validated over the concentration ranges of 1–500 ng/ml for diazepam, 0.25–50 ng/ml for atropine and 5–1000 ng/ml for pralidoxime. The coefficients of variation were always &lt;15% for both intra-day and inter-day precision for each analyte. Mean accuracies were also within ±15%. This method has been successfully applied to a pharmacokinetic study of the three compounds after intramuscular injection of an avizafone–atropine–pralidoxime combination, in healthy subjects