Conferenceseries Joint International Event on 7^th Pharmacovigilance & Pharmaceutical Industry August 22-24, 2016 Vienna, Austria

Chrissy Cochran completed her PhD from University of Maryland Baltimore and postdoctoral studies from Johns Hopkins University School of Public Health. She is the director of the Division of Enforcement and Postmarketing Safety, in the Office of Compliance, Center for Drug Evaluation and Research, U.S. Food and Drug Administration. She has published more than 10 papers in reputed journals and presented more than 30 abstracts.

In September 2013, the United States Food and Drug Administration’s (US FDA) Commissioner began an initiative to organize US FDA inspectors along regulated commodity areas, such as pharmaceutical or device manufacturing, food processing, or bioresearch monitoring (human subject protection, clinical trial data reliability, compliance with US FDA postmarketing safety regulations). Increased specialization and dedication of inspectors in the bioresearch monitoring program will result in inspectors gaining more in-depth knowledge of regulations and industry practices and trends. This will enable inspectors to refine the unique skills needed to conduct inspections, and provide reliable data to support the US FDA’s decision to approve US FDA regulated products. In turn, the change will result in higher quality inspections of US FDA regulated products. The poster presentation will discuss the objectives of the bioresearch monitoring program, purpose of the Commissioner’s initiative, and the plan to implement a vertically integrated commodity based program. The outcome of the Commissioner's initiative is greater protection of public health regarding US FDA regulated products.

Mario Bertazzoli is a physician and a registered specialist in Human Reproduction Pathology. He received both medical and specialization degrees from the University of Milan, Italy. He worked since 1995 for international pharmaceutical companies as pharmacovigilance and pharmaco-epidemiology physician. He is currently the Head of Corporate Drug Safety and Reference Physician to the EU Qualified Person for Pharmacovigilance for the Helsinn Group. He is founder and treasurer of the International Society of Pharmacovigilance, Swiss-Austrian Chapter.

A continuous evaluation of the positive therapeutic effects of a medicinal product in relation to the risks is of paramount relevance also for a mature drug that has been on the market from many years. Regulatory Authorities may at any time ask the marketing authorization holder to forward data demonstrating that the benefit-risk balance remains favourable and it is continuously assessed. Nimesulide is a COX-2 preferential NSAID characterized by a particularly rapid onset of analgesic action. The widespread nimesulide post-marketing use has contributed to better understand its favourable safety profile. However, the extensive use of a drug poses unique challenges since even a rare but severe risk can have a significant impact on the population. A safety referral under Article 31 (Directive 2001/83/EC) may be initiated in specific cases where the interest of the public health in the European Union is involved, for example following concerns related to the benefit-risk balance of a medicinal product.The actions taken to keep the possible risk under control regarded the conduction of non-interventional studies, education of prescribers on the correct use of the drug and risk minimization actions.The efficacy of these actions has been monitored through drug utilization studies that have shown how nimesulide is, in the vast majority of cases, prescribed according to the approved label.

Tomasz Ząbkowski has obtained a Doctor’s Diploma in Medicine, Faculty of Medicine, Military Medical University in Lodz in 1991, a Diploma of First Grade of Specialization in Surgery, Military Medical University in Warsaw in 1994, a Diploma of Doctor of Philosophy in Medicine in 1995 and a Diploma of Second Grade of Specialization in Urology in 1997. He is the adjunct professor in Urology Department, Military Institute of Medicine in Warsaw. He has published more than 102 papers in Polish journals and 14 papers in reputed journals and has been serving as an editorial board member of Pharmacist’s Journal in Warsaw. He is a permanent reviewer of international scientific journal American Journal of Case Reports and he reviewed scientific works for international scientific journals, such as Urology Journal of the Urology and Nephrology Research Center and Medical Science Monitor.

Background: α-1-adrenolytics contribute to decreasing urinary symptoms by improving objective parameters, increasing maximum urine flow rate and decreasing urine retention after miction. The selective α 1-AR blockers relieve obstruction by relaxing the smooth muscle in the prostate and bladder neck. The most common drugs available from this class are doxazosin, tamsulosin, alfuzosin and terazosin. The aim of this study was to evaluate the mechanism of action of α-1-adrenolytics in combination therapy with finasteride in patients diagnosed with BPH. Material & Methods: The clinical trial was conducted in 2 stages: Stage I from October 2008 to November 2009 and Stage II from November 2009 to November 2010. A total of 10, 066 patients, n1=4315 and n2=5751, respectively for each stage were enrolled in 50 urological centers in Poland participating in the clinical trial. Results: The analyzed group, in which the combination drug therapy was prescribed on the second visit, included 6408/10,066 (63.05%) patients. On the third visit following the administration of an α-1-adrenolytic, attenuation of BPH symptoms were observed in 3882/6 408 (60.58%) patients. Conclusions: α-1-adrenolytics showed high efficiency in decreasing dysuric discomforts, improving objective parameters, increasing maximum flow rate and decreasing residual urine after miction.

Prof. Dr. Manal M. Kandeel, Professor of Pharmaceutical Organic Chemistry at the Faculty of Pharmacy, Cairo University and currently Vice Dean for Postgraduate Studies and Research Affairs, at the Faculty of Pharmaceutical Sciences and Pharmaceutical Industries, Future University, Egypt. Formerly, I held several positions including Vice Dean for Postgraduate Studies and Research Affairs, and for Community Service and Environment as well, at the Faculty of Pharmacy, Cairo University.My primary research area of interest is design, synthesis, structure elucidation, and development of anticonvulsant, antimicrobial and anticancer agents. I published numerous articles in various national and international journals.

Inhibition of tubulin polymerization is one of the important tactics in cancer therapy. Since 4-aryl-4Hchromene derivatives are found to be microtubule-binding agents via interfering with tubulin polymerization so we decide to concentrate our exploration efforts on the combination of this nucleus with 5-, 6-, and/or 7-memebered heterocyclic moieties in a novel series of compounds to explore the effect that might result from this combination. Ten novel compounds were selected for anticancer screening assay against MCF-7 breast cancer cell line in comparison to colchicine as positive control and most of them showed excellent activity.

YL Chen has completed her PhD at the age of 29 years from National Taiwan University. She is a Professor of Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University. She has published more than 80 papers in reputed journals.

Aliskiren is a direct renin inhibitor that has been effective in attenuating hypertension. The aim of this study was to determine whether aliskiren could protect the ischemia-induced myocardial infarction (MI) and elucidate the mechanisms of action. C57J/BL6 mice were subjected to the ligation of left anterior coronary artery and were treated for14 days with vehicle or aliskiren (25 mg/Kg/day via an subcutaneous injection), whereas sham-operated animals served as controls. Aliskiren improved systolic and diastolic LV function and improved cardiac morphology compared with PBS-treated mice after MI. This was associated with the number of TUNEL-positive cells. Alikiren increased autophagy assayed by LC3B-II expression and transmission electron microscopy. Furthermore, we employed H9c2 cardiomyocytes as a cell model to investigate the effects of aliskiren on apoptosis and autophagy in cardiomyocytes under hypoxia-induced injury of cardiomyocytes. H9c2 cells were treated with 1- 20 M aliskiren for 24 h under normoxia, none of which had significant effect on the cell viability by MTT assay. 80% of cells died after hypoxia for 16 h, while aliskiren treatment rescued cell death in a dose-dependent manner. In all subsequent experiments, unless otherwise specified, 20 μM aliskiren was used. The beneficial effects of aliskiren were associated with the decrease of apoptosis and the increase of autophagy by increased autophagosomes. Taken together, our findings revealed that aliskiren increased cardiomyocyte survival through the increased autophagosomal formation.

Shahinaze Amry was graduated from the Faculty of Pharmacy, Cairo University. She has completed her Master of Sciences degree in 2013 from Cairo University, Egypt. She is an assistant lecturer and PHD student in the Department of Pharmaceutics and Industrial Pharmacy, Ahram Canadian University. She published two papers in the International Journal of Pharmaceutics and presented posters in many international conferences, one of which is the AAPS in November 2013, in Texas,USA

Dapoxetine (D) suffers from poor oral bioavailability (42%) due to extensive first pass metabolism. The usefulness of transmucosal (sublingual and intranasal) drug delivery to improve bioavailability of D, a weak basic drug, has been hampered by its poor solubility in the neutral pH of the body fluids. In this study, instantly-soluble transmucosal matrices (ISTMs) of D, containing dual mechanism solubilizer (Pluronic F-127/citric acid mixture), were prepared by lyophilization technique to enhance matrix disintegration, dissolution and transmucosal permeation. The matrices were evaluated for in-vitro disintegration, wetting time, in-vitro dissolution, ex vivo transmucosal permeation, scanning electron microscopy and in-vivo studies. Dissolution studies confirmed the higher ability of ISTMs to enhance the early time point dissolution and maintain complete drug dissolution in pH 6.8 compared to conventional lyophilized matrices. The optimized ISTM gave approximately 77.54 and 88.40 folds increase of D dissolution after 1 and 3 min relative to the drug powder in pH 6.8. ISTMs containing the highest F127 concentration (2%) and the lowest gelatin and mannitol concentrations (1%) exhibited the shortest in-vitro disintegration times ( < 10 s), the fastest dissolution in the neutral pH of body fluids (≈ 99% in 3 min) and the highest enhancement of transmucosal permeation. The relative bioavailabilities of D after sublingual and intranasal administration of ISTMs to rabbits were about 124.58% and 611.15%, respectively, in comparison to the oral market tablet. The significant increase of drug dissolution in nasal fluids, rapid permeation rate together with the improved bioavailability propose that ISTMs could be promising for intranasal delivery of drugs suffering from oral hepatic metabolism and have limited solubility in nasal fluids.

Kamran Fazel has completed his MD at the age of 25years from Isfahan University of Medical Sciences. He postgraduated in anesthesia and critical care medicine at 2012 from Bagiatalla University of Medical Sciences and has completed fellowship in critical care medicine from Isfahan University School of Medicine at 2014. He has published 5 papers in reputed journals.

Management of difficult to wean patients is a dilemma for health care system. Recent studies demonstrated efficacy of donepezil to counteract respiratory depression in sleep apnea.However,pharmaceutical interventions with donepezil to facilitate weaning have not been tested so far.In this non-randomized interventional clinical study,we evaluated the efficacy of using donepezil on weaning course in difficult to wean(eligible) patients. Eligible patients with prior inappropriately depressed respiratory responses were included from two referral ICUs in Iran.Other potentially reasons of weaning failure were excluded.Donepezil was started at dose of 10 mg daily for 2–4weeks.For the primary outcomes,arterial blood gas(ABG)parameters were also measured before and after intervention.Weaning outcomes of patients were reported as final outcome.Twelve out of16studied patients had successful results to facilitate weaning.The mean duration of donepezil treatment until outcome measurement was12days.There were not any significant differences in ABG parameters among patients with successful and failed weaning trial on day of donepezil initiation. However after intervention,mean of PCO2 and HCO3 decreased in patients with successful weaning trial and mean of PCO2 increased in those with weaning failure.Reduced central respiratory drive was infrequently reason of failed weaning attempts but it must be considered especially in patients with hypercapnia secondary to inefficient gas exchange and slow breathing.The results suggest that,the use of donepezil can expedite weaning presumably by stimulation of respiratory center and obviate the need to re-intubation in cases of respiratory drive problem in these patients.We suggest decrease PCO2 and HCO3 during donepezil steady could be valuable predictors for positive response to donepezil intervention.