Stability study of cefepime in NaCl at different storage times and temperaturesA Ressault, A Schavgoulidze, P GandiaCHU – Toulouse (France)Introduction: Cefepime is an antibiotic of choice for the treatment of joint prosthesis infections given its good bone tissue penetration 1. Because of physico‐chemical instability during continuous administration, cefepime perfusion should be changed every 8 h 2. This is an expensive constraint in terms of medical costs, particularly for patients treated at home.

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The aim of this study was to document the stability of cefepime reconstituted solutions at several temperatures (+4°C, +25°C, +33°C) and over various storage periods (8, 12, 24 h).Material and methodsThree intravenous infusion solutions were prepared using 1 g of cefepime in 50 mL of NaCl. The initial (baseline) concentration was measured before storing the solutions at temperatures of + 4, +25 or +33°C, respectively.

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The concentrations and percentage degradation of cefepime were determined (in triplicate); cefepime degradation exceeding 10% was the evaluation criterion for physico‐chemical instability. Samples were diluted in 1:200 and analysed using LC‐UV methodology with 3‐point calibration ranging from 1 to 200 mg/L.Results: Cefepime stability was maintained for 24 h at + 4°C and + 25°C, and for 12 h at + 33°C. Moreover, a yellow coloration was present at + 25°C and + 33°C after 24 and 12 h, respectively.Discussion/Conclusion: Our results show that the optimal conditions for storing cefepime in a portable diffuser is 12‐h at + 25°C.

Indeed, cefepime degradation is acceptable up to 12 h (. Voriconazole chronic underexposure in a non‐extensive metabolizer treated for disseminated Scedosporium prolificans infection: which pharmacological approach to increase voriconazole drug level?C Boglione‐Kerrien a, MC Verdier a, E Gautier‐Veyret b, B Hennart c, S Belaz d, M Revest e, A Petitcollin a, C Tron a, JP Gangneux d, E Bellissant a, F Lemaitre aaRennes University Hospital, Department of Clinical and Biological Pharmacology and Pharmacovigilance, Pharmacoepidemiology and Drug Information Centre – Rennes (France), bUniv. Grenoble Alpes, Inserm, CHU Grenoble Alpes, HP2 – Grenoble (France), cLille University Hospital, Department of Pharmacology and Toxicology – Lille (France), dRennes University Hospital, Department of Mycology‐Parasitology – Rennes (France), eRennes University Hospital, Department of Infectious Diseases and Intensive Care Unit – Rennes (France)Introduction: Voriconazole underexposure is detrimental to the clinical efficacy of the antifungal treatment, particularly during life‐threatening invasive fungal infections (IFI). Based on the case of a patient treated for a Scedosporium prolificans infection, we report the pharmacological approach aiming at improving voriconazole exposure.Material and methodsA 61‐year‐old Caucasian man who was autografted with hematopoietic stem cell from peripheral blood, due to a multiple myeloma IgG kappa, presented with an IFI at the end of aplasia.

Scedosporium prolificans was documented, associated with a right eye infection and a meningitis with brain abscess. An antifungal triple therapy regimen with oral voriconazole (200 mg twice daily (BID) following the loading dose), combined with terbinafine and miltefosine was initiated. Good treatment compliance and absence of any drug‐drug interactions with a Cytochrome P450 inducer were verified. Therapeutic drug monitoring (TDM) of voriconazole trough concentrations (Cmin) was conducted, completed by a pharmacogenetics approach.Results: Increased dosages did not allow increasing Cmin which remained stable around 1.40 μg/mL (dosage up to 400 mg BID) and then decreased to 0.90 μg/mL (500 mg BID). The addition of lansoprazole, a CYP2C19 inhibitor, had no real impact on voriconazole exposure. To overcome a possible malabsorption problem, it was decided to switch to the intravenous route.

As Cmin remained weak, a greater activation of the secondary metabolic pathway by CYP3A4 or 3A5 was suggested: grapefruit juice was chosen to inhibit CYP3A. Concentrations slightly increased to reach trough values up to 1.90 μg/mL for approximately 3 weeks before decreasing again. CYP2C19 genotyping revealed a non‐extensive metabolizer profile while CYP3A4 and CYP3A5 genes sequencing did not show any polymorphism resulting in an accelerated metabolism. Genetic variants of the Flavin‐Containing Monooxygenase 3 (FMO3) have also been explored revealing polymorphisms which might lead to a decrease in voriconazole concentrations.Discussion/Conclusion: TDM was an essential tool but did not entirely allow ensuring adequate voriconazole exposure. Among the possible explanations, the hypothesis of an auto‐induction of voriconazole metabolism, which has already been proposed in previously published papers, could be raised. A combined genotyping of the CYP2C19, CYP3A4, CYP3A5 and FMO3 genes could be of relevance in the patient's management in case of voriconazole chronic underexposure. Benzodiazepine withdrawal in elderly: what prevalence, what signs, which patients?

Population pharmacokinetic analysis and limited sampling strategy of ofloxacin in patients with bone and joint infectionsJB Foulquier, A Petitcollin, F Fily, M Revest, MC Verdier, P Tattevin, JL Polard, D Huten, C Arvieux, E Bellissant, B Laviolle, F LemaitreCHU – Rennes (France)Introduction: Ofloxacin is one of the recommended treatments for bone and joint infections. Fluoroquinolones’ efficacy is related to the area under the curve of their blood concentrations (AUC0‐24 h) over the minimum inhibitory concentration (MIC) for a given bacteria. Hence, the drug exposure appears as a crucial determinant of its efficacy and it could be useful to evaluate these parameters using therapeutic drug monitoring (TDM).

There is a paucity of data for ofloxacin in patients infected with gram positive bacteria which is maybe the most common situation in OAI. The aim of the present study is to describe the pharmacokinetics of oral ofloxacin and, from the model obtained, to establish a limited sampling strategy (LSS) to estimate AUC0‐τ and to determine an optimization a priori of the dosing regimen in these patients.Material and methods: Pharmacokinetics of ofloxacin was described using a compartmental modeling with population approach using the software Monolix. The D‐optimality, Bayesian and Multiple Linear Regression approaches were used to determine the LSS.

Every 30 min.

Incompatible: Dual-layer, thus fails to install correctly. Can be installed via PC, but songs on the second layer will cause the game to lock up.

The fix:. Extract files from the ISO with Apache 3.

Free Mcboot Hdd Loader

Open ISO with ISOBUSTER and saved FILELIST.TXT in the extracted folder (right click on the small red ISO icon select Directory tree and file information then select List tree-info (in text file) then select LBA,relative path),. Move MAIN3, 4, and 5.ARK to GEN folder. Edit FILELIST.TXT and add lines for MAIN3, 4, and 5.ARK, with the same LBA listed in APACHE 3 and same path of MAIN2.ARK.

Open CDGenPS2 and selected Import Tree File, ISOBuster from the Advanced menu. Select FILELIST.TXT from the game folder. Used LBA, no fix or something.

Saved the image.