Formulation and stability study of a pediatric 2% phenylephrine hydrochloride eye drop solution.

INTRODUCTION: We present formulation and stability evaluation of a 2% (w/v) phenylephrine hydrochloride biocompatible eye drop solution, routinely prepared in hospital pharmacy under aseptic conditions, for retinal examination of neonates and premature infants. MATERIALS AND METHODS: Eye drop solution was formulated by dissolution of phenylephrine hydrochloride and disodium hydrogen phosphate as buffering agent in sterile water for injection and sodium chloride for injection as isotonic agent. The previous solution was sterile filtered through under aseptic conditions, in an iso class 5 air quality clean room under horizontal laminar airflow hood. Physical stability (visual inspection, osmolality measurements), chemical stability (pH measurement, phenylephrine assay by liquid chromatography coupled with an ultra-high resolution and accurate mass) and sterility evaluation of phenylephrine eye drop solution stored at ambient temperature were studied during 60 days. RESULTS AND DISCUSSION: The formulated eye drop solution had a pH of 6.90±0.05 and an osmolality of 285±2 mOsm/kg. Throughout the 60 days study the solutions remained clear without any precipitation or color modification, sterility was maintained, pH and osmolality were not significantly modified and no significant loss of product was detected using liquid chromatography coupled with an ultra-high resolution and accurate mass instrument suggesting the lack of degradation. CONCLUSION: These results indicate that 2% phenylephrine hydrochloride eye drop solutions were physically, chemically and microbiologically stable for at least 60 days when stored in type I amber glass vials at room temperature, allowing the compounding of higher batch sizes.

Assessment of interindividual variability of plasma concentrations after administrazion of high doses of intravenous amoxicillin or cloxacillin in critically ill patients.

The aim of the present retrospective observational clinical study was to assess the interindividual pharmacokinetic variability of plasma concentrations of amoxicillin or cloxacillin administered in high doses intravenously in critically ill patients, related to renal function or administration method.Four hundred and two plasma concentrations were measured at steady-state with a high performance liquid chromatography technique in 162 patients treated with 100 - 300 mg/kg/day of intravenous amoxicillin or cloxacillin.For both drugs and administration methods, plasma concentrations were significantly higher for patients with creatinine clearance below 60 ml/min, even though doses were adapted for renal impairment. the correlations calculated between plasma concentrations and creatinine level, creatinine clearance or doses were all low. There were fewer outlying drug concentrations in patients receiving continuous rather than intermittent regimens.Our results are in favor of adapting dosages of these beta-lactam antibiotics based on plasma concentrations, especially in cases of renal impairment.

Use of high-performance liquid chromatography (HPLC) to monitor beta-lactam plasma concentrations during the treatment of endocarditis.

Guidelines recommend high doses of beta-lactams for the therapy of endocarditis. This report describes a retrospective study of 15 endocarditis patients (median age 64 years), treated according to guidelines, whose beta-lactam trough plasma concentrations were measured with high-performance liquid chromatography because of tolerance or efficacy concerns. For amoxycillin, the mean level was 86.8 mg/L (range: 30-212 mg/L); five (45%) patients had concentrations > 1000 x MIC. For cloxacillin, the mean level was 47.9 mg/L (range: 16.7-104 mg/L). The consequences of high and unpredicted beta-lactam trough plasma concentrations for a prolonged period have not yet been thoroughly evaluated.

[An experience in teaching pharmacology on the internet]. / Une expérience d'enseignement de la pharmacologie par Internet.

Internet and Intranet are omnipresent in the University world. We developed an easy-access website (www.med.univ-rennes1.fr/etud/pharmaco) devoted to teaching pharmacology and report here our experience after 4 years of use. Our objective was to determine the value of this new teaching tool in the medical coursus. The site is entirely free and presents approximately 50 topics and diaporamas discussing various themes: the cell, the receptor, general pharmacology, clinical research, population research, drug classes, etc. Harbored by the Medical Informatics Laboratory of the University of Rennes Medical School, this site serves as a reference for medical students and others. More than 100 visits are recorded daily, approximately half from visitors outside France. The advantages of this new teaching tool, which operates within the framework of a Virtual Medical University project, are evident for students and professors alike. Its impact on the quality of drug therapy by future doctors remains to be determined.

Role of dopaminergic and serotonergic systems on behavioral stimulatory effects of low-dose alprazolam and lorazepam.

Several recent studies have demonstrated that alprazolam and lorazepam, administered at low doses to healthy volunteers, improve cognitive functions and psychomotor performances. Paradoxical effects of low-dose benzodiazepines have been also observed in mice, in experimental pharmacology. The aim of this work was to determine, in rat, the effect of similar low-doses of benzodiazepines on spontaneous locomotor activity and performance in the elevated zero-maze, and to investigate the underlying neurobiological mechanisms. The dose-effect and the time-course of the action were studied for both compounds. Spontaneous locomotor activity was measured using a photoelectric actimeter. The level of anxiety of the animals was assessed in the elevated zero-maze. Dopamine, serotonin, and their metabolites were assayed in the extracellular striatal fluid of the awake rat, obtained by microdialysis, by HPLC--EC. Spontaneous locomotor activity observed in rats given low-dose alprazolam and lorazepam evidenced a stimulatory effect only with alprazolam. The effect was maximum 90 min after administration of 0.0050 mg/kg alprazolam. An anxiogenic-like action was evidenced with the elevated zero-maze for the two compounds. We observed a statistically significant increase in striatal dopamine concentrations only with alprazolam, during the period corresponding to the behavioral stimulatory effects. We also showed a marked trend towards increased levels of serotonin with alprazolam but this modification was not significant, in spite of statistically significant variations of 5-HIAA. In the rat, behavioral stimulatory effects of low-dose benzodiazepines is evidenced with alprazolam but not lorazepam. This effect could be explained, at least in part, by increased extracellular dopamine concentrations in the striatum. Their different structures could explain the different pattern observed for the two benzodiazepines.

[Perspectives for drug treatment in Alzheimer's disease]. / Perspectives médicamenteuses dans la maladie d'Alzheimer.

The last decade was very fruitful in neuropharmacology and notably in the therapeutic strategies of dementia and Alzheimer's disease (AD). The amount of data, information and breakthroughs is nevertheless difficult to apply in direct relationship with patients. The present review aims at classifying information according to their origins: epidemiology, clinical trials, neurosciences. A guide for drug prescription in Alzheimer's disease is thus warranted and becomes clearer, sure that, in the next future modifications and new strategies will appear. The main goal of the present review is to summarize the state-of-the-art for a non specialist in AD.