Interaction of drugs used in gynecology and urology and their management Author: Kupka Vojtěch Tutor: PharmDr. Martin Doseděl Ph.D., Department of Social and Clinical Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Králové Introduction: Drug interactions represent a serious health problem and they cause adverse drug effects and toxicity of drugs. Objectives: The goal of the thesis was to create an overview of possible drug interactions with drugs used in gynecological and urological practice. Methodology: From a theroretical introduction was selected registred drugs to 1 st January 2015 by State Institute for Drug Controle. Information about drug interactions were collected and collated from databases Vademecum Infopharm and Micromedex. From database Micromedex, the drug interactions were selected with quality of documentation "excellent" or "good". Pubmed database (www.pubmed.gov) with entering key words "basic drug", "drug interaction" and "interactive drug" was applied to create a current information. To complement the information was also gathered from magazines Practical Pharmacy and Clinical Pharmacology and Pharmacy. In case of not finding relevant information was drawn from the summary information of medicine (SPC). Results: The results were categorized into a research...

1 Abstract Charles University in Prague, Faculty of Pharmacy in Hradci Králové Department of: Pharmaceutical Technology Consultant: doc. PharmDr. Zdeňka Šklubalová, Ph.D. Student: Lucie Pospěchová Title of Thesis: Dosage forms in therapy of posterior segments of the eye. Therapy of the posterior eye segments is very difficult. Because most of diseases of the posterior eye segments could lead to complete blindness, the research of dosage forms for the drug delivery into this eye part is intensively developing at this moment. The aim of this thesis is to provide a review of anatomical and physiological specifics of both- anterior and posterior segments of the eye. The most common diseases of the posterior eye are referred to, for example the age related macular degeneration and/or the cytomegalovirus retinitis. There are various routes of application and drug dosage forms that are used for the therapy and which are mentioned in this work, including the drug delivery and targeting systems.

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Patrícia Čečková Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Study of drug interactions with OATP family transporters using intestinal tissue slices An essential role in the action of orally administered drugs is their absorption through the intestinal barrier. It expresses a variety of transporters, including the OATP2B1 and OATP1A2 influx transporters, belonging to the SLC family. They are located on the apical membrane of enterocytes and allow the flow of endogenous and exogenous substances from the lumen of the intestines to the enterocyte. They affect not only the pharmacokinetics of drugs, but also their safety and efficacy. They represent sites of drug interactions with other drugs/food components that may altered drug efficacy or toxicity. Since FDA (The Food and Drug Administration) and EMA (European Medicines Agency) do not have intestinal OATP transporters included in their guidelines for preclinical studies, there is no single model of interaction study. The limitations of cell models and genetically modified organisms lead to the development of new methods such as the ex vivo method of precision cut intestinal slices (PCIS), which represents a tissue model...

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Lenka Ťupová Supervisor: doc. PharmDr. Martina Čečková, Ph.D. Title of doctoral thesis: Interactions of selected antiretroviral drugs and methylmercury with placental membrane transporters. Pregnant women are especially in developed countries exposed to high amount of various xenobiotic including environmental pollutants and drugs. Antiretroviral therapy (ART) is administered to HIV positive pregnant women for the purpose of prevention of HIV mother- to-child-transmission. Pharmacokinetics of many antiretrovirals is limited or enhanced by activity of ATP-binding cassette (ABC) or Solute carrier's transporters, of which many are expressed also in placental tissue. ART therapy usually consists of combination of 3 - 4 antiretroviral drugs, thereby leading to higher risk for development of drug-drug interactions on ABC and SLC transporters. In this study we described influence of non-nucleoside reverse transcriptase inhibitors etravirin and rilpivirin on BCRP- and MDR1-mediated transport of tenofovir disoproxil fumarate (TDF) and/or abacavir. Etravirin showed potent inhibition of BCRP transporter significantly changing transport of both, TDF and abacavir, across monolayers of MDCKII-BCRP...

Charles University, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Ondřej Martinec Supervisor: Assoc. Prof. PharmDr. Lukáš Červený, Ph.D. Title of doctoral thesis: Interactions of antiretroviral drugs with membrane transporters Oral delivery is the most common, convenient, and economical form of drug administration. Absorption of orally administered drugs occurs mainly in the intestine. Intestinal absorption can be reduced by the activity of efflux drug ABC transporters, mainly p-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2), located in the apical membrane of the intestinal epithelium. HIV-infected patients are dependent on lifelong pharmacotherapy, which includes a combination of three or more antiretroviral drugs. Hepatitis C (HCV) is a common co-infection of HIV. In addition, the HIV-positive population is aging, which is associated with burden of other comorbidities. This results in an indication of polypharmacy and thus an increased risk of drug-drug interactions. Many antiretroviral drugs used are substrates, inhibitors and /or inducers of ABCB1, so they might quantitatively affect the intestinal absorption of co-administered drugs (ABCB1 substrates), thereby affecting the efficacy/safety of treatment. As part of this...

Candidate: Kateřina Kukrálová1 Supervisor: prof. RNDr. Jiří Vlček, CSc.1 Consultant: PharmDr. Zuzana Očovská1 1 Department Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University Title of the master thesis: The analysis of drug-drug interactions in patients admitted to hospital (I.) The presence of potential drug-drug interactions (DDIs) is common in daily practice and only a small proportion of potential DDIs results in hospitalization of the patients. Nevertheless, DDIs represent a significant cause of hospital admissions. This study aims to identify DDIs in the medication history of the patients admitted to University Hospital Hradec Králové via the emergency department in August-November 2018. The objectives of this study are a) to determine the prevalence of potential DDIs; b) to categorize identified potential DDIs with respect to their mechanism, severity, risk rating, level of documentation and potential outcomes and c) to determine the prevalence of manifest DDIs. This study has a cross-sectional design. The following data were obtained retrospectively from electronic medical records: demographic data, medication history, past medical history, laboratory and clinical findings, and information about hospital admission. The identification of potential DDI was...

Charles University Faculty of Pharmacy in Hradec Kralove Department of Pharmacology & Toxicology Student: Gabriela Burianova Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Flow-cytometric analysis of inhibitory effect of novel targeted drugs on the activity of ABC drug efflux transporters Cancer is the second leading cause of death. Cancer treatment often combines conventional chemotherapy, radiation therapy and surgery. More recent approach to treatment is the use of targeted cancer therapy with a greater specificity towards cancer cells. Development of resistance is a major obstacle in the success of chemotherapy. Multidrug resistance (MDR) can be acquired through various mechanisms e.g. overexpression of efflux transporters. ATP binding cassette (ABC) transporters represents a large family of transmembrane proteins that use ATP to pump molecules across the membrane. The three main ABC proteins related to MDR are: P-glycoprotein (ABCB1), multidrug resistance-associated protein 1 (ABCC1) and breast cancer resistance protein (ABCG2). Use of ABC transporter inhibitors increases the amount of chemotherapeutical substrates accumulated within the cells. In this study we evaluated interactions of six synthetic small molecule inhibitors (alisertib, ensartinib, entrectinib, talazoparib,...

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Lucia Dziaková Supervisor: RNDr. Jakub Hofman, Ph.D. Title of diploma thesis: Study on interactions of PARP inhibitors with ABC drug efflux transporters. ATP-binding cassette (ABC) transporters are integral membrane proteins that use the energy obtained from ATP to carry transport of numerous endogenous substrances out of the cells, but attention is drawn primarily to the fact that they transfer also xenobiotics. Their overexpression in tumor tissue contributes to multidrug resistance (MDR), which in most cases leads to therapy failure. Poly(ADP-ribose)polymerase inhibitors (PARPi) represent a promising therapeutic approach in the treatment of cancers that exhibit defects in homologous recombination (HR). This work focuses on four selected PARPi (olaparib, rucaparib, niraparib, veliparib) and their interaction potential towards ABC drug efflux transporters (ABCB, ABCC1, ABCG2). In our work, we worked with MDCKII cells (parent, transduced by the transporters of interest) and utilized the principle of accumulation studies based on the measurement of fluorescence intensity of specific model substrates (hoechst33342, calcein AM, daunorubicin, mitoxantrone). We used established inhibitors of studied...

Drug Information Centre service analysis IV. - drug interactions Author: Georg Michálek Supervisor: PharmDr. Kateřina Malá, Ph.D. Consultant: PharmDr. Petra Rozsívalová Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic Introduction: Drug information centre (DIC) of the Faculty of Pharmacy in Hradec Králové, Charles University, and University Hospital Hradec Králové was established in 1994. It provides drug information to healthcare professionals in the form of timely and accurate answers to drug-related enquiries, including drug interactions (DI). Aim: This study aimed to analyse enquiries related to DI processed by DIC from 2015 to 2020 and to solve three drug enquiries related to drug interactions. Methods: Quantitative and qualitative analysis of drug enquiries was carried out. Data was collected from individual enquiries related, but not limited to drug-drug, drug-herbal, and drug-disease interactions. The quantitative analysis based on descriptive statistical methods was performed on two levels: enquiry level and drug interaction level. On the enquiry level, ATC codes found in the enquiries were analysed and on the drug interaction level various parameters assigned to each DI were analysed, such as interacting components,...

The theoretical part of this diploma work is focused on the polymeric nanoparticles, their properties and advantages connected with them. There are introduced also particular types of organic and inorganic nanoparticles and methods of their preparation. The great attention was directed on biodegradable polymers in particular to poly lactic-co-glycolic acid, which was used in experimental part as carrier for base of terbinafine branched to tripentaerythritol. PLGA is the most suitable copolymer for practice because of good explored its physical, chemical and biological properties, methods of preparation and factors affecting degradation. The aim of this work was to find suitable emulsifier with suitable concentration for preparation of nanoparticles containing the base of terbinafine, suitable solvent for terpolymer and optimal concentration of emulsion to reach the highest yield of terbinafine without any exceptional loss. How it was mentioned, as carrier was used terpolymer of poly lactic-co-glycolic acid with tripentaerythritol. As technique of preparation of nanoparticles was used emulsification by evaporating of organic solvent (solvent evaporation method). During the experimental work we found out some of conclusions, it goes to reduce of polydispersity with increasing concentration of...