[The prevention of noise inducted hearing loss: the new challenge of active electronic hearing protection].

Based on today's common hearing aid design and technology, the team of researchers successfully designed a DPI which allows the worker to be "protected" against loudness and in the same time guarantee a good level of communication and perception of the surrounding environment. The design of this new device is very much similar to a standard BTE hearing aid which allows the use of an active DPI very comfortable, robust and easy to use. The research using the prototypes was divided into 3 phases: Phase 1: 24 volunteers coming from non-industry companies did undergo a specific trial protocol.

Therapeutic drug monitoring of posaconazole in hematology adults under posaconazole prophylaxis: influence of food intake.

Posaconazole (PCZ) is given at 200 mg three times daily as a fungal prophylaxis in neutropenic hematologic malignancy patients. A relationship between exposure, plasma concentration, and efficacy is suggested. The objectives of this prospective study were to analyze the PCZ plasma concentration in hematology adults at high risk of developing invasive fungal infections (IFIs), and factors that could have an impact on the PCZ plasma concentration.

Pharmacokinetic variability of voriconazole and N-oxide voriconazole measured as therapeutic drug monitoring.

Voriconazole (VRC), a triazole agent is extensively metabolized by CYP2C19, CYP2C9, and to a lesser extent, by CYP3A4. Few data are available regarding disposition of the main VRC metabolite (MVRC; UK121,265). The aim of this study was to investigate the pharmacokinetic variability of VRC and MVRC plasma concentrations on the basis of 115 drug monitoring samples from patients treated with VRC.

Posaconazole-increased vincristine neurotoxicity in a child: a case report.

A 9-year-old girl was managed according to the COPRALL 04 protocol for treatment of a relapse of acute lymphoblastic leukemia. Owing to a previous case of disseminated fusariosis, posaconazole was started 5 days before initiation of chemotherapy. Six days after the last dose of vincristine, the child reported symptoms of severe peripheral neuropathy, abdominal cramps, and constipation.

Inherited long QT syndrome revealed by antifungals drug-drug interaction.

A 14-year-old Tahitian girl with acute myeloid leukaemia and a suspected mucormucosis infection was treated with intravenous voriconazole and caspofungin. Because of worsening of fungal infection, voriconazole was switched to posaconazole. During the switch, the patient presented with QT interval prolongation with 'torsades de pointes' and reversible cardiac arrest.

Adverse effects of voriconazole: analysis of the French Pharmacovigilance Database.

Background: The most common adverse effects of voriconazole reported during clinical trials were disturbances of vision (30% of pts.), skin rashes (17.3%), and elevations in hepatic enzymes level (approximately 10% of pts.

Variability in the clinical pattern of cutaneous side-effects of drugs with systemic symptoms: does a DRESS syndrome really exist?

Objective: To improve the definition of the various clinical patterns of patients with drug-induced cutaneous side-effects with systemic symptoms, and their possible relationships with the triggering medication, with the ultimate goal of helping in the identification of the causal drug in difficult situations when the patient is taking several drugs.

Methods: Cases of drug-induced cutaneous side-effects associated with various systemic syndromes related to anticonvulsants (carbamazepine, phenytoin and phenobarbitone), minocycline, allopurinol, abacavir and nevirapine were collected retrospectively from the French Pharmacovigilance database (FPD) over a period of 15 years (1985-2000). The clinical patterns typical of the causative drugs were described and compared with data from the literature.

Neurotoxicity related to valganciclovir in a child with impaired renal function: usefulness of therapeutic drug monitoring.

Objective: To report a case of neurotoxicity related to antiviral drugs, discuss the involvement of concomitant medications, and document the pharmacokinetics of ganciclovir (administered as valganciclovir) in a child with impaired renal function.

Case Summary: A 13-year-old boy with acute lymphoblastic leukemia was treated for cytomegalovirus retinitis with valganciclovir 450 mg every 2 days in the course of hematopoietic stem cell transplantation. Concomitant medication included omeprazole, furosemide, and acetaminophen.

Liquid chromatography-electrospray mass spectrometry determination of carbamazepine, oxcarbazepine and eight of their metabolites in human plasma.

Carbamazepine (CBZ) and oxcarbazepine (OXCBZ) are both antiepileptic drugs, which are prescribed as first-line drugs for the treatment of partial and generalized tonic-clonic epileptic seizures. In this paper, a specific and sensitive liquid chromatography-electrospray ionization mass spectrometry method was described for the simultaneous determination of carbamazepine (CBZ), oxcarbazepine (OXCBZ) and eight of their metabolites [CBZ-10,11-epoxide (CBZ-EP), 10,11-dihydro-10,11-trans-dihydroxy-carbamazepine (DiOH-CBZ), 10-hydroxy-10,11-dihydroCBZ (10-OH-CBZ), 2-hydroxycarbamazepine (2-OH-CBZ), 3-hydroxycarbamazepine (3-OH-CBZ), iminostilbene (IM), acridone (AO) and acridine (AI)] in human plasma. The work-up procedure involved a simple precipitation with acetone.

Optimal management of methotrexate intoxication in a child with osteosarcoma.

Objective: To describe the time course and management of methotrexate (MTX) toxicity in a 14-year-old Hispanic boy with osteosarcoma treated with high-dose MTX.

Case Summary: During the sixth cycle of high-dose MTX, severe intoxication was observed with high MTX plasma concentrations, acute renal failure, and hepatitis, followed by mucositis and moderate myelosuppression. Intensification of urine alkalinization and increased leucovorin dosages did not decrease plasma concentrations of MTX or prevent systemic toxicities.

Performance analysis of a rapid HPLC determination with the solvent demixing extraction of HIV antiproteases and efavirenz in plasma.

A rapid and simple high-performance liquid chromatographic method without internal standardization is evaluated for the drug-level monitoring of most marketed antiproteases and efavirenz. Following plasma deproteinization with acetonitrile, the analytes are extracted into the solvent while it is demixed by the addition of a saturating amount of neutral salt. The organic supernatant is diluted by half with water up to the polarity of the mobile phase before being injected.

Application of a standardized coextractive cleanup procedure to routine high-performance liquid chromatography assays of teicoplanin and ganciclovir in plasma.

Deproteinization of plasma samples with acetonitrile followed by coextracting acetonitrile and lipophilic solutes with chloroform, as already proposed for methotrexate, is stressed as a general sample cleanup procedure for liquid chromatography of highly polar drugs, and was validated for two more applications: teicoplanin and ganciclovir. A dedicated "prevalidation" experimental design was used to assess performances of both assays, including sample preparation. Deviations from linearity were less than 10% over the ranges of 3.

Prevalidation statistical design to assess analytical methods. Example of a quick liquid chromatographic assay of itraconazole in serum.

(A) An analysis-of-variance spreadsheet program is presented which allows to readily test and/or quantitate in a single run analytical linearity, matrix effect on recovery, repeatability of measurement and of extraction and the ruggedness of these features for up to three sessions. Owing to napierian logarithmic transformation, ANOVA mean squares directly read as relative standard deviations and checking linearity is straightforward. (B) A quick assay for therapeutic drug monitoring of itraconazole and its main metabolite was devised with the help of the program, and subsequently validated according to current quality control recommendations.

High-performance liquid chromatographic determination of fluconazole in plasma.

A high-performance liquid chromatographic method with ultraviolet absorbance detection at 260 nm was developed for the analysis of fluconazole in plasma. The method involves sample clean-up by liquid-liquid extraction. The proposed technique is reproducible, selective, reliable and sensitive.

Determination of methotrexate and 7-hydroxymethotrexate by liquid chromatography for routine monitoring of plasma levels.

A high-performance liquid chromatographic (HPLC) method was designed to meet analytical and metrological requirements for routine blood level monitoring of methotrexate (MTX) and its main metabolite 7-hydroxymethotrexate (7OMTX). The metabolite, unavailable as a pure substance, was measured by reference to MTX calibration according to their respective ultraviolet absorbances. Acetonitrile deproteinization and chloroform clean-up provided plasma samples devoid of long-retained contaminants.

High-performance liquid chromatographic determination of cis-dichlorodiammineplatinum(II) in plasma ultrafiltrate.

A reproducible, simple and sensitive high-performance liquid chromatographic method was described for the quantitative analysis of cis-diamminedichloroplatinum(II) (CDDP) in ultrafiltrate plasma in the presence of nickel chloride as internal standard. CDDP and the internal standard were chelated by exchange with diethyldithiocarbamate. After derivatization, the mixture was directly injected into the column.

Performance analysis of a reversed-phase liquid chromatographic assay of lamotrigine in plasma using solvent-demixing extraction.

A reversed-phase column liquid chromatographic assay is described and validated for lamotrigine, a new anticonvulsant drug. The drug and its internal standard were extracted from plasma into acetonitrile according to a previously described solvent-demixing procedure, separated on LiChrospher 100CN, and measured by ultraviolet absorption at 280 nm. The assay performance was evaluated through analysis of variance and of regression with our usual validation design.

Pharmacokinetics of an indomethacin pro-drug: apyramide after intravenous administration in dog.

The pharmacokinetics of apyramide, an ester of indomethacin and acetaminophen (paracetamol), were determined after intravenous administration to nine beagle dogs. Indomethacin and its pro-drug, apyramide, were extracted from acetonitrile-precipitated plasma by a solvent-demixing procedure and the concentration of these two drugs was measured by a reversed-phase liquid chromatographic assay. The kinetic evolution with time of plasma levels of apyramide and of indomethacin resulting from enzymatic hydrolysis was compared with values obtained for indomethacin injected in equimolar dose.

Carbamazepine and its 10,11-epoxide metabolite in acute mania: clinical and pharmacokinetic correlates.

The study was designed to investigate the antimanic profile of carbamazepine as a first-line drug in affective or schizoaffective disorders, to correlate the clinical efficacy with the plasma level of carbamazepine and its 10,11-epoxide metabolite, and to test the potential value of monitoring the salivary level. It was administered alone for 3 weeks to 21 acute manic inpatients. During the first week, the dosage was rapidly increased to 800 mg/day in order to produce steady-state plasma levels of carbamazepine on Day 7.

Liquid chromatographic assay of heptaminol in serum and its oral pharmacokinetics in the dog.

In order to investigate the pharmacokinetics of heptaminol in dogs, a high-performance liquid chromatographic assay of the drug was devised and it was evaluated in a general purpose validation design through analysis of variance. Heptaminol and its internal standard n-propylamine were salted out from plasma together with acetonitrile, the previously proposed "solvent demixing " extraction procedure. Both amines were derivatised in acetonitrile with the o-phthaldialdehyde, 2-mercaptoethanol procedure of Roth.