Day :
- Pharmacological Sciences | Pharma Consulting & Services | Bio-Pharmaceutics | Bioinformatics Pharmaceutical Chemistry
Location: LEON
Chair
Solomon Habtemariam
University of Greenwich, UK
Co-Chair
Anna Szemik-Hojniak
University of Wroclaw & University of Applied Sciences-Walbrzych, Poland
Session Introduction
Maria A Miteva
University Paris Diderot, France
Title: Pharmacogenomics of cytochrome P450: Effects of missense mutations on drug metabolism
Biography:
Maria A Miteva has completed her PhD in 2000 at the Bulgarian Academy of Science. She has vast experience on bioinformatics, chemoinformatics, in silico drug design and pharmacology. She is a Research Director at Inserm Institute and a Leader of the team “Virtual screening, PPI & ADMET in silico” (MTi, Insem U973, Paris Diderot University). She has published over 80 scientific articles in peer-reviewed journals and she has edited a book “In silico Lead Discovery” (Bentham Sci). Currently, she is an appointed Member of the Editorial Board of 5 international journals in the field of Bioinformatics and Drug Design and Associated Editor for BMC Pharmacology Toxicology.
Abstract:
Pharmacogenomics investigates DNA and RNA variations in the human genome related to drug responses. Cytochrome P450 (CYP) is a supergene family of drug metabolizing enzymes responsible for the metabolism of approximately 90% of human drugs. Among the major CYP isoforms, the CYP2C subfamily is of clinical significance because it metabolizes approximately 20% of clinically administrated drugs and represents several variant alleles leading to adverse drug reactions or altering drug efficacy. Recent progress on understanding the inter-individual variability of the CYP2C members and the functional and clinical impact on drug metabolism will be presented. The structural bases and molecular mechanisms of amino acid variants of CYP2C members that affect drug metabolism will be discussed.
Khalid Awad Al-Kubaisi
University of Gloucestershire, UK
Title: Identifying risk factors for incautious use of non-prescription drugs among university students in Emirates
Biography:
Al Kubaisi is a post-gradute researcher in his final year of PhD program in Public Health from Gloucestershire University, UK. He awarded his master degree, Excellent with First Honours, in Public Health (MPH) from Hamadan bin Mohamed Smart University, Dubai during the academic year 2010- 2012. He attended his under graduate school at the University of Baghdad where he received his Bachelor degree in Science of Pharmacy in 1996. He spent ten years working as a pharmacist in UAE. His research’s interest is in self-medication practice and in the use of non-prescription drugs by university’s students. For example, investigating students’’ behavior towards reading the drug information leaflets. Recently, he developed and evaluated an Educational Intervention designed for modifying university students’ practice, knowledge, awareness and attitude in favor of responsible self-medication.
Abstract:
Background: Use of non-prescription drugs (NPD) among university students is a serious public health issue. Previous study has reported that generally, a sizeable proportion of consumers do not read the drug information leaflet (DIL) before using NPD. However, few studies have identified the risk associated with not reading drug information leaflet before using NPD. There are no extensive studies, which measured the prevalence and identified the risk associated with not reading DIL among university students. Therefore, we attempted to fill the gap in the literature.
Methodology: A cross-sectional survey-based study was conducted from January to April 2014, among 2875 students in three randomly selected UAE universities. A structured and validated questionnaire was used to collect the responses of the students. SPSS version 20 was used to analyze the data.
Results: More than half (1348; 57%) of participants reported using of Oral NPD. Of 1348 participants reported using Oral NPD, one quarter (1348; 22.2%) of Oral NPD was classified as incautious Oral NPD usage as they did not read the DIL while using the medication for the first time. This study has identified 10 risk factors for incautious Oral NPD use. Participants with age group of 21 years and older (OR=0.554, 95% CI: 0.373-0.823) (p<0.001), female (OR=0.339, 95% CI:0.236-0.486) (p<0.001), and students from medical schools (OR=0.619, 95% CI: 0.435-0.882, p value=0.008) had lower odds of being incautious users compared to lower age group, males and students from non-medical schools. Furthermore, participants with a polypharmacy behaviour had higher odds of being incautious Oral NPD user than monopharmacy users (OR=1.400, 95% CI: 1.030-1.02) (p<0.001).
Conclusion: There a few incautious Oral NPD use among university students, but it is a serious issue when it comes to medical students. There is a need for raising awareness among all medical students to motivate them to be cautious users because they are going to be the future healthcare providers. Further studies are required to explore other risk factors.
Young Chul Kim
Seoul National University, South Korea
Title: Protective effect of Betaine against Galactosamine-induced acute hepatic injury in rats
Biography:
Young C Kim is a Professor of Toxicology at Seoul National University, College of Pharmacy, since 1986. He received his MS and PhD from Purdue University and completed Post-doctoral research at the National Institute of Environmental Health Sciences (NIEHS), NIH, USA. He has published more than 100 papers in reputed journals. He is a recipient of several prestigious international and national awards including the Thieme Most Innovative Original Paper Award at GA, Society for Medicinal Plant and Natural Product Research, and the Korean Teachers’ Award.
Abstract:
Statement of the Problem: Galactosamine (GalN) is a potent hepatotoxicant that inhibits RNA and protein synthesis via depletion of uridine nucleotide in the liver. Earlier studies suggested that some endogenous sulfur-containing substances, particularly glutathione (GSH) and/or S-adenosylmethionine (SAM), might antagonize the induction of liver injury by GalN. In this study, we determined the effect of betaine, a methyl donor used for remethylation of homocysteine to methionine, against GalN-induced acute liver injury in association with alterations in the metabolomics of sulfur-containing amino acids and related substances in the liver.
Methodology: Male Sprague-Dawley rats received betaine (1% in drinking water) for 2 wk prior to GalN challenge (400 mg/ kg, ip). Rats were sacrificed 24 h later for the assay.
Findings: GalN treatment elevated serum alanine transaminase (ALT), aspartate transaminase (AST), and sorbitol dehydrogenase (SDH) activities significantly, and these changes were blocked by betaine supplementation. Histopathological examination revealed extensive multifocal necrosis with macrophage infiltration in liver of the GalN-treated rats, which was also inhibited by betaine supplementation. GalN treatment increased methionine, but not SAM levels in the liver. Betaine supplementation further increased the hepatic levels of methionine, SAM, and methionine adenosyltransferase (MAT) activity. Hepatic GSH contents were not altered by betaine or GalN. GalN treatment elevated ornithine and spermidine, but decreased putrescine levels in the liver, suggesting that the metabolic conversion of ornithine to putrescine was impaired. Betaine supplementation increased hepatic putrescine and spermidine significantly, but ornithine levels were unaltered. LDH leakage increased progressively for 24 h after GalN treatment in H4IIE cells, which was inhibited almost completely by betaine or SAM addition.
Conclusion & Significance: The results suggest that the hepatoprotective effect of betaine against GalN-induced liver injury may be associated with an enhancement of polyamine biosynthesis via induction of MAT activity and SAM availability in the liver.
Arik Dahan
Ben-Gurion University of the Negev, Israel
Title: The complexity of intestinal permeability and its implications on oral drug absorption and bioavailablity
Biography:
Arik Dahan is an Associate Professor of Pharmaceutics and Biopharmaceutics at the Department of Clinical Pharmacology and the School of Pharmacy, Ben-Gurion University of the Negev in Beer-Sheva, Israel. He is also an Adjunct Professor of Pharmaceutical Sciences at the College of Pharmacy, University of Michigan, USA. He received his PhD (2007) from the Hebrew University of Jerusalem. From 2007 until 2009, he was a Post-Doctoral Research Fellow at the University of Michigan College of Pharmacy with Professor Gordon Amidon. His research interest is the integration of up-to-date molecular and cellular mechanistic investigations of drug disposition in the context of the human body, in order to enable successful drug delivery and therapy. In implementing this molecular biopharmaceutical approach to ADME research, he is seeking to enable mechanistic-based successful solutions to drug delivery, especially (but not only) oral, in challenging scenarios e.g. low-solubility, low-permeability, efflux transport, extensive metabolism, poor site targeting, various pathophysiological conditions (e.g. obesity, inflammatory bowel disease), and pediatrics patient care. He has authored over 70 top-notch journal papers, and contributed chapters to 7 books.
Abstract:
In this lecture, regional-dependent intestinal permeability will be discussed, including dissolution aspects, as well as pathophysiological conditions. Permeability is location dependent, and pertains to each point throughout the gastrointestinal tract. A drug may exhibit significantly different intestinal permeability not only between the small and large intestine, but even within the small intestine, i.e. between the proximal jejunum and the distal ileum. The asymmetrical pH profile throughout the small intestine may be the underling mechanism for such segmental-dependent permeability of certain ionizable drugs. An asymmetrical expression pattern of different transporters throughout the intestinal tract may also cause such regional-dependent permeability. Asymmetrical intestinal enzymes expression may significantly influence the systemic bioavailability of a drug, although not necessarily affect the permeability. In these cases, rapid vs. sustained dissolving drug products may result unexpectedly different systemic drug levels. In conclusion, it is prudent to consider the intestinal permeability pattern when deciding on a certain dissolution profile.
Tuba Aydin
Agri Ibrahim Cecen University, Turkey
Title: Inhibition effects of Tarragon (Artemisia dracunculus L.) extracts and its metabolites against the carbonic anhydrase I and II isozymes
Biography:
Tuba Aydin is currently working as an Assistant Professor in the Faculty of Pharmacy at the Agri Ibrahim Cecen University, Turkey where she has been a faculty member since 2013. She completed her PhD at Ataturk University, Turkey. She has expertise in isolation and characterization of phytochemicals from natural products.
Abstract:
Tarragon, Artemisia dracunculus L. is a small shrub and perennial plant species. It spreads in Japan, India, Iran, Europe, North America and China. The plant has several medicinal properties. It used in making vinegar and salad. In this study, five metabolites were isolated from dichloromethane extract from tarragon and their the chemical structure was characterized as anethole (1), β-stigmasterol (2), herniarin (3), (2E,4E)-N-isobutylundeca-2,4-dien-8,10-diynamide (4) and (2E,4E)-1- (piperidin-1-yl)undeca-2,4-diene-8,10-diyn-1-one (5) by IR, 1D and 2D NMR spectroscopic methods. Enzyme inhibition activities of ethanol, dichloromethane, n-hexane and methanol extracts of A. dracunculus L. and all of the pure metabolites were investigated against human carbonic anhydrase I and II isoenzymes. Enzyme inhibition effects of the extracts and pure metabolites were evaluated by comparison of their IC50 values for the first time in this study. Our results showed that the extracts and the pure compounds of A. dracunculus L. were found to be strong inhibitor against the human carbonic anhydrase I and II isoenzymes. The compounds and extracts were showed in the range of 8.65-486.2 μM of IC50 values for Carbonic anhydrase I and II.
Hussam AS Murad
King Abdulaziz University, Saudi Arabia
Title: Impact of combined inhalation of Roflumilast or formoterol plus fluticasone on matrix metalloproteinase-9 and its inhibitor in ovalbumin-asthmatic mice
Biography:
Hussam Murad worked as a Professor at Pharmacology and Clinical Pharmacy Departments in a number of universities in Egypt and Saudi Arabia. He has an experience of about 25 years in teaching and research. He has worked in 10 research projects as a Principal Investigator and as a first Co-investigator in another four. He has got funds from King Abdulaziz City for Science and Technology (KACST), Riyad, SA, and Deanship of Scientific Research, King Abdulaziz University (KAU), Jeddah, SA. He received the award of scientific publication from KAU, in 2015 and in 2017.
Abstract:
Statement of the Problem: In a recently-published work, we concluded that co-inhalation of roflumilast+fluticasone more significantly improved inflammatory and histopathological changes than co-inhalation of formoterol+fluticasone in ovalbumin-asthmatic mice. The matrix metalloproteinase-9 (MMP-9) is the principal MMP involved in pathogenesis of asthma, and thus its inhibition could be beneficial to protect against airway inflammation and remodeling. This study was designed in ovalbumin-asthmatic mice to investigate effects of inhaled roflumilast and formoterol alone or combined with fluticasone on levels of matrix metalloproteinase-9 (MMP-9) and its tissue inhibitor-1 (TIMP-1) in the bronchoalveolar lavage fluid (BALF).
Methodology & Theoretical Orientation: Asthma was induced in female BALB/c mice by ovalbumin sensitization and challenge. In addition to the normal control (NC) group, the ovalbumin-asthmatic mice were randomly divided into seven groups (n=8): positive control (PC), vehicle-treated, and five drug-treated groups. Treatments (μg/kg) were given as 15 min-inhalation once/day for seven days as follows: roflumilast (R, 500), formoterol (Fo, 50), fluticasone (F, 1000), roflumilast+fluticasone (R+F, 500+1000), and formoterol+fluticasone (Fo+F, 50+1000).
Findings: The PC mice showed significant increases of the levels of MMP-9 and TIMP-1 in the BALF compared to the NC group. All treatments (except formoterol) significantly decreased these ovalbumin-induced changes mainly with the R+F group which showed a non-significant difference from the NC group. The combinations were significantly different from monotherapies and the R+F group was significantly different from the Fo+F group.
Conclusion & Significance: Co-inhalation of roflumilast+fluticasone more significantly improved the BALF levels of MMP- 9 and TIMP-1 than co-inhalation of formoterol+fluticasone in the ovalbumin-asthmatic mice. Recommendations of adding inhaled roflumilast to inhaled corticosteroids could be beneficial in treatment of asthma due to its antiinflammatory and antifibrotic effects.
- Types of Pharmaceutical Formulations | Hospital Pharmacy | Pharmacognosy and Phytochemistry
Location: LEON
Co-Chair
Arik Dahan
Ben-Gurion University of the Negev, Israel
Session Introduction
Irina Ermolina
De Montfort University, UK
Title: Characterization of mechanical properties of freeze-dried cake in vial: Application for Pharmaceutical formulation development
Biography:
Irina Ermolina obtained her PhD degree in molecular physics and after 15 years of work in biophysics she expanded her interests into the pharmaceutical science. After post-doc positions at University of Jerusalem and University of Glasgow she got a senior lectureship at De Montfort University, UK. Irina Ermolina has her expertise in Pharmaceutical and Biological Materials Science (especially. amorphous materials); Drug Delivery Systems (hydrogels); Process Analytical Technologies for Pharmaceutical Manufacture (esp. Freeze-Drying and Roller Compaction); and different analytical techniques (Dielectric Relaxation Spectroscopy, Terahertz Imaging and Terahertz Spectroscopy, Thermoanalytical methods). She has published 48 articles and book chapters.
Abstract:
Freeze-drying (FD), or lyophilisation, is a standard commonly used method for the production of long-term stable solid products. The most frequently used containers for freeze-drying are glass vials and blister packs. The aim of this study was to develop and optimize a Texture Analysis (TA) technique to study the compressive mechanical properties of FD cakes directly in glass vials using a standard commercially available texture analyser. Examining the cakes in glass vials has many advantages as it allows studying the intact FD cakes minimizing the bias from texture distortion during samples preparation, and reducing the moisture uptake. The mechanical properties of the FD cakes can provide valuable information on the strength and susceptibility to breakage of the FD cakes, in particular, when developing the formulation for the orally disintegrating tablets. Besides, analysis of the mechanical properties and the texture of the FD cakes can help improve the freeze-drying protocols as the properties of FD cakes (in particular, the pore size and the wall thickness of FD solids) depend on the FD cycle parameters. The application of a standard texture analysis (TA) technique to study the mechanical properties of the freeze-dried cakes directly in glass vials used for freeze-drying has been demonstrated. A procedure allowing quantitative assessment of the strength, fracturability, and elastic properties of the FD cakes using TA has been developed. The results show that the TA method is sensitive to the variations in cake materials, storage conditions (temperature, excessive moisture), and cake quality. The results also show that TA can also be applied for optimization and improvement of the freeze-drying protocols and rapid disintegrating tablet formulation development.
Jitka RychlÃÄková
Hospital Na Bulovce, The Czech Republic
Title: Clinical pharmacy service at orthopedic department in the Czech Republic
Biography:
Jitka RychlíÄková works as a Clinical Pharmacist at Hospital Na Bulovce, Prague, she has been assigned to Orthopedic Department for four years. She is a PhD candidate in the field of Safety and Quality of Drugs where she deals with economic evaluation of clinical pharmacy services. As a member of the board of the Czech Society of Clinical Pharmacy, she contributes to clinical pharmacy developing in the Czech Republic. She is interested in teaching and is a Lecturer in Continuous Pharmacy and Clinical Pharmacy Education, as well as she teaches Pharmacology to Under-graduate Medical students.
Abstract:
Statement of the Problem: In the Czech Republic the clinical pharmacy is a young and rapidly growing field. One of the Czech clinical pharmacy authorities predefined some general procedures how to provide clinical pharmacy; three levels of clinical pharmacy services were predefined. Previously published data to the topic of clinical pharmacy services in orthopedics and traumatology departments are very scarce. The aim is to present results of clinical pharmacy service at orthopedic/traumatology department as an example of application of predefined procedures.
Methodology & Theoretical Orientation: We have been collecting data during four years of continuous cooperation. At the department (with 7 units) the combination of all three levels of clinical pharmacy services was applied.
Findings: Our results provide an evidence of increasing orthopedists’ adherence to newly introduced clinical pharmacy service during four years as well as provide an evidence of professional growth of clinical pharmacist herself. On the first level of clinical pharmacy services the clinical pharmacist does an intervention in 17% of admitted patients at this type of department, the most interventions are associated with antithrombotics and the recommendation to continue the unchanged therapy is becoming the most common intervention during the four-year period. On the second level of clinical pharmacy services the analgesic therapy was improved by elimination of an off-label drug, moreover hydration regimen and prevention of chemotherapy induced nausea and vomiting was optimized. On the third level some rules for prescription were established.
Conclusion & Significance: There is evidence how the general predefined procedures work, their application to the orthopedic/ traumatology department is shown and their efficacy in here is presented. There is enough space for clinical pharmacy services even in orthopedics/traumatology.
Tuba Aydin
Agri Ibrahim Cecen University, Turkey
Title: Effects of some natural compounds on the glutathione reductase enzyme
Biography:
Tuba Aydin is currently working as an Assistant Professor in the Faculty of Pharmacy at the Agri Ibrahim Cecen University, Turkey where she has been a faculty member since 2013. She completed her PhD at Ataturk University, Turkey. She has expertise in isolation and characterization of phytochemicals from natural products.
Abstract:
Discovery of Glutathione Reductase (GR) inhibitors has become very popular recently due to antimalarial and anticancer activities. In this study, GR inhibitory capacities of some natural compounds, β-sitosterol, β-stigmasterol, diosgenin and jervine, which have steroidal skeleton, were reported. While β-stigmasterol was isolated from Artemisia dracunculus, β-sitosterol, diosgenin and jervine were isolated from rhizomes of Veratrum album. The chemical structures of the compounds were confirmed by IR, 1H-NMR, 13C-NMR, 1D and 2D NMR methods. The tested molecules were exhibited much potent inhibitory activities against GR at low micromolar concentrations with IC50 values ranging from 0.1916 to 5.2116 μM as compared with well-known agents. In this study first time, the inhibition effects of β-sitosterol, β-stigmasterol, diosgenin and jervine were determined on glutathione reductase enzyme.
Fatma Tugce Guragac
Gazi University, Turkey
Title: Insights into research on the anti-inflammatory and antinociceptive activities of Scandix iberica Bieb.
Biography:
Abstract:
It is thought that bioactive compounds from plant foods may have beneficial health effects and decrease the risk of chronic inflammatory diseases. In Turkish folk medicine, flowers of the Scandix iberica Bieb. (Apiaceae) have been used to combat rheumatic pain. The aim of this study is to appraise the anti-inflammatory and antinociceptive activities of the different types of extracts prepared from S. iberica carrageenan, Prostaglandin E2 (PGE2) and serotonin-induced hind-paw oedema, acetic acid-induced capillary permeability and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced mouse-ear oedema models were used to appraise anti-inflammatory activity. Antinociceptive activity was tested using a p-benzoquinone induced abdominal constriction method. Among the extracts, only the n-Hexane extract was shown to possess a noticeable anti-inflammatory and antinociceptive activity in mice without inducing any gastric damage at 100 and 200 mg/kg doses, while the rest of the extracts were entirely inactive. The activity of the n-Hexane extract led to a greater appreciation of some phenylpropanoids, mainly estragole (88.90 %), through Capillary Gas chromatography-Mass Spectrometry (GC-MS).