Physical-chemical stability of docetaxel concentrated solution during one month

Background  Docetaxel is an antineoplastic agent widely used in combination with others cytotoxic agents in many cancers (breast cancer, non-small cell lung cancer, prostate cancer, etc.). Today, this costly cytotoxic agent is marketed by several pharmaceutical companies who suggest discarding any remainder immediately after use, making it a very costly drug. Purpose  The aim of this study was to determine the physical-chemical stability of docetaxel stock solution after the first sampling in the vial. Materials and methods  The study was conducted in accordance with European consensus guidelines for the practical stability of anticancer drugs (1) and by two societies GERPAC and SFPC (2). The physical-chemical stability was assessed on 3 different vials of docetaxel (Taxotere 20 mg/mL). On day 0, 2, 4 and 30 triplicate samples of each vial of docetaxel were assayed by a high performance liquid chromatography (HPLC) method with UV detection at 230 nm (method validated following ICH guidelines). Docetaxel concentration at day 0 was considered to be 100% and if the docetaxel concentrations in samples were greater than 90% in the following days they were considered stable. The reference concentration was degraded by 20% by addition of a quantity of 0.01N NaOH in order to produce and observe primary degradation products. On each vial and on different days, docetaxel UV absorption spectra between 200 and 600 nm, pH and colour change were compared by a visual inspection with reference at T = 0, and finally a turbidimetry method at 350, 410 and 530 nm was used to evaluate the formation of visible and sub-visible particles. Results  After 30 days, for each sample, no colour or pH change were observed, all UV spectra and turbidimetry measures were strictly similar. From day 2 to day 30, docetaxel concentrations were not significantly different to the day 0 solution and no degradation products were observed in any samples. According to these results, no significant drug loss was shown during the study period. Conclusions  At a storage temperature between 20 to 25°C for 30 days, docetaxel solution at 20 mg/mL was seen to be stable. The sterility of the solution was not tested because the handling environment (Iso 5) was strictly controlled and operator validations are regularly checked

An island based hybrid evolutionary algorithm for optimization

This is a post-print version of the article - Copyright @ 2008 Springer-VerlagEvolutionary computation has become an important problem solving methodology among the set of search and optimization techniques. Recently, more and more different evolutionary techniques have been developed, especially hybrid evolutionary algorithms. This paper proposes an island based hybrid evolutionary algorithm (IHEA) for optimization, which is based on Particle swarm optimization (PSO), Fast Evolutionary Programming (FEP), and Estimation of Distribution Algorithm (EDA). Within IHEA, an island model is designed to cooperatively search for the global optima in search space. By combining the strengths of the three component algorithms, IHEA greatly improves the optimization performance of the three basic algorithms. Experimental results demonstrate that IHEA outperforms all the three component algorithms on the test problems.This work was supported by the Engineering and Physical Sciences Research Council (EPSRC) of UK under Grant EP/E060722/1

Evolution entre 2007 et 2009 de la résistance des Entérobactéries et de Pseudomonas aeruginosa à la ciprofloxacine, en fonction de la consommation de fluoroquinolones au CHU d'Angers

National audienc

Evolution entre 2007 et 2009 de la résistance de Pseudomonas aeruginosa à la ciprofloxacine en fonction de la consommation des fluoroquinolones au CHU d'Angers

National audienc

Drug related problems and pharmacist interventions in a geriatric unit employing electronic prescribing

Background Computerised physician order entry (CPOE) and the integration of a pharmacist in clinical wards have been shown to prevent drug related problems (DRPs). Objectives The primary objective was to make an inventory of the DRPs and resident pharmacist on-ward interventions (PIs) identified in a geriatric acute care unit using CPOE system. The secondary objective was to evaluate the physicians\u27 acceptance of the proposed interventions. Setting A 26-bed geriatric ward of a 1,300-bed teaching hospital. Method A 6-month descriptive study with prescription analysis and recommendations to physicians by a resident pharmacist during five half days a week. Main outcome measures Patients\u27 characteristics, number of prescribed drugs per patient, nature and frequency of DRPs and PIs, physicians\u27 acceptance and drugs questioned. Results Resident pharmacist reviewed 311 patients and identified 241 DRPs. One hundred and fifty-two patients (49 %) had at least one DRP (mean +/- A SD age 87 +/- A 6 years, mean +/- A SD number of prescribed drugs 10.7 +/- A 3.4). Most frequent DRPs were: untreated indication (n = 58, 24.1 %), dose too high (n = 46, 19.1 %), improper administration (n = 31, 12.9 %) and drug interactions (n = 23, 9.5 %). The rate of physicians\u27 acceptance was 90.0 % (7.5 % refusals, 2.5 % not assessable). DRPs related to CPOE system misuse (n = 35, 14.5 %) appeared as a worrying phenomenon (e.g., errors in selecting dosage or unit, or duplication of therapy). Conclusion A resident pharmacist detected various DRPs. Most PIs were accepted. DRPs related to the misuse of the CPOE system appeared potentially dangerous and need particular attention by healthcare professionals. The description of the DRPs is an essential step for implementation of targeted clinical pharmacy services in order to optimize pharmacists\u27 job time

Restoration of Macroscopic Isotropy on (d+1)(d+1)-Simplex Fractal Conductor Networks

Restoration of macroscopic isotropy has been investigated in (d+1)-simplex fractal conductor networks via exact real space renormalization group transformations. Using some theorems of fixed point theory, it has been shown very rigoroursly that the macroscopic conductivity becomes isotropic for large scales and anisotropy vanishes with a scaling exponent which is computed exactly for arbitrary values of d and decimation numbers b=2,3,4 and 5.Comment: 27 Pages, 3 Figure

Higher Order Effects in the Dielectric Constant of Percolative Metal-Insulator Systems above the Critical Point

The dielectric constant of a conductor-insulator mixture shows a pronounced maximum above the critical volume concentration. Further experimental evidence is presented as well as a theoretical consideration based on a phenomenological equation. Explicit expressions are given for the position of the maximum in terms of scaling parameters and the (complex) conductances of the conductor and insulator. In order to fit some of the data, a volume fraction dependent expression for the conductivity of the more highly conductive component is introduced.Comment: 4 pages, Latex, 4 postscript (*.epsi) files submitted to Phys Rev.