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Physiological and pathological factors affecting absorption of drugs
Ryšánek, Pavel ; Šíma, Martin (advisor) ; Mičuda, Stanislav (referee) ; Dražanová, Eva (referee)
Absorption of drugs from the gastrointestinal tract after oral administration is a key pharmacokinetic process co-determining the subsequent pharmacodynamic response of the organism and therapeutic efficacy. This dissertation thesis is devoted to the study of factors that influence this parameter. Special emphasis is placed on the study of lymphatic absorption, i.e. the rate of absorption of the active substance via the intestinal lymphatic system. A number of in vivo studies have been carried out in laboratory rats. Pharmacokinetic studies have been performed by means of regular blood sampling from vascular catheters after oral administration of the drug. Lymphatic absorption was investigated in an anaesthetized mesenteric lymphatic duct cannulated rat model. Modern drugs were tested that were incorporated into innovative dosage forms by collaborating chemical and technological institutions. Abiraterone acetate, a lipophilic agent used in the therapy of prostate cancer, was well absorbed from the gastrointestinal tract after administration in the form of oil marbles. This technology also succeeded in reducing the otherwise very significant positive food-effect. Abiraterone acetate was not absorbed to any significant extent via the intestinal lymphatic system. In contrast, lymphatic absorption of...
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Identification of opportunities and threats for the selected company
ŠÍMA, Martin
The diploma thesis deals with opportunities and threats identification in a particular company. To detect its opportunities and threats, the company has to analyse micro and macro environment, at first. In order to analyse company's macro environment, the STEP analysis is used. The STEP analysis facilitates external factors identification and its possible effects on a company in the near future. The micro environment analysis is carried out by The Porter's model of five competitive forces in the industry, supplemented by points and comparison of the largest competitors. At the same time, An analysis of selected financial indicators is performed, which together with Porter's model of five competitive forces in the sector reveals the company's strengths and weaknesses. After processing all the information and subsequent evaluation using SWOT analysis, recommendations are proposed. These eliminate hidden threats and take advantage of the opportunities, which the agency employment market undoubtedly offers.
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Applied pharmacokinetics in preclinical research
Královičová, Jana ; Šíma, Martin (advisor) ; Večeřa, Rostislav (referee) ; Kmoníčková, Eva (referee) ; Paluch, Zoltán (referee)
Title: Applied pharmacokinetics in preclinical research Author: Mgr. Jana Královičová Abstract: This thesis addresses the topic of development and practical utilization of rat models in preclinical pharmacokinetic studies. An analysis dealing with the impact of intra- and inter- individual variability on the results of animal comparative studies showed that cross-over design brings more accurate conclusions in these experiments than the often-used parallel setting. Results obtained on the basis of a parallel design significantly differed in our investigation (AUClast ranged from 9.62 to 44.62 mg/ml.min.g). Furthermore, in 4 cases out of 15 pair comparisons of individual parallel groups, the confidence interval did not include the 100% value. That means that in more than a quarter of studies it would be misjudged that the compared drug formulations have different pharmacokinetic properties, though they are in fact the same product. The practical use of cross-over design is demonstrated in pharmacokinetic studies comparing the absorption of various formulations with abiraterone and cinacalcet. In a fasted state, a new, innovated formulation with abiraterone was better absorbed than the reference (AUClast of a reference 30.3 mg/ml.min.g, innovated formulation 81.0 mg/ml.min.g). Thiscorresponds to anticipations...
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Customer satisfaction with offer of services of golf courses in Prague and in Liberec region
Šíma, Martin ; Čáslavová, Eva (advisor) ; Ruda, Tomáš (referee)
Title: Customer satisfaction with offer of services of golf courses in Prague and in Liberec region Objectives: The Diploma Thesis aims to make a survey of satisfaction and expectations of golf course customers in Liberec region and in the capital city Prague and to compare those regions. Customer satisfaction will be measured by means of questionnaires where each player of each golf course will compare real perceived qualities of a golf course with generally expected qualities. Based on the data obtained, the analysis of values will be carried on, such as golf handicap, age, gender and month income. The Thesis will focus on comparing the expectations and satisfaction of major golf resorts with smaller and not so popular ones. Methods: The research of customer satisfaction was carried on by already proven questionnaire consisting of SERVQUAL method. The research compared expected quality with real quality in seven golf courses in Prague and surroundings and in seven golf courses in Liberec region. The research was carried on from August 2014 till February 2015. Results: The outcome of the thesis is to learn about satisfaction of golfers at golf courses in Prague and Liberec region and submit proposals for improving each golf courses in an effort to achieve improved and better access to customers....
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Isosters of transkarbam 12 as transdermal penetration enhancers
Šíma, Martin ; Hrabálek, Alexandr (advisor) ; Vávrová, Kateřina (referee)
SUMMARY: Diploma thesis - Isosters of Transkarbam 12 as skin penetration enhancers Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium-5-(dodecyloxycarbo- nyl)pentylcarbamate, T12) is a highly effective skin permeation enhancer. In this diploma thesis, T12 analogs with carbamate and carbonate function groups replacing the ester one were synthetised, and evaluated in vitro as skin permeation enhancers on excised porcine skin, using theophiline as a model drug. The results were expressed by an enhancing ratio and compared with the biological activity of T12. The enhancing activity decreases in the following sequence: ester, carbonate, carbamate. The results thus show that it is the ester group in the molecule of T12 which is essential for its extraordinary effect. In addition, homologues with a different length of the ending and connecting carbon chains were evaluated. While the length of the connecting carbon chain does not influence the biological activity significantly, nonyl to decyl ending carbon chains show the highest acceleration ability. It indicates that the length of the carbon chain, and not its lipofility, is important for the enhancing activity.
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Asymetrically substituted ureas as a skin permeation enhancers
Šíma, Martin ; Hrabálek, Alexandr (advisor) ; Vávrová, Kateřina (referee)
PharmDr. Martin Šíma Asymetrically substituted ureas as a skin permeation enhancers ABSTRACT: Transkarbam 12 (5-(dodecyloxycarbonyl)pentylammonium-5-(dodecyloxycarbo-nyl)pentylcarbamate, T12) is a highly effective skin permeation enhancer. In this rigorous thesis, T12 analogs with urea function group replacing the ester one were synthetised, and evaluated in vitro as skin permeation enhancers on excised porcine skin, using theophiline as a model drug. The results were expressed by an enhancing ratio and compared with biological activity of T12 and its analogs from previous studies (alkane, ketone, amide, carbamate, and carbonate). Similarly to analogs from previous studies, there was a significant decrease in the enhancing potency. The results thus show that the ester group in the molecule of T12 is essential for its extraordinary effect.
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Statistical learning and client risk assessment
Šíma, Martin ; Pešta, Michal (advisor) ; Mazurová, Lucie (referee)
This bachelor thesis tackles model selection for classification problems and presents binary logistic regression. A method of parameter estimation is discussed and the necessity of numerical approach is explained, iteratively reweighted least squares method is used. The Wald and Wilks tests are defined to measure statistical significance of the parameters. The difference between qualitative and quantitative data and their interpretation is discussed. Model selection method of the stepwise selection is defined, residual plots and other methods of the model fit measurement are introduced. Acquired knowledge is applied to a data set of bank clients.
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Factors affecting drug distribution and elimination and their application in personalized pharmacotherapy.
Šíma, Martin ; Slanař, Ondřej (advisor) ; Juřica, Jan (referee) ; Tesfaye, Hundie (referee)
The aim of this dissertation thesis was to study the factors affecting drug distribution and elimination and to use these factors to individualize dosing. The work consists of three thematic areas: estimation of the volume of distribution and subsequent dosing of selected drugs (vancomycin, amikacin, phenobarbital) using body size descriptors; estimation of clearance and subsequent dosing of selected drugs (vancomycin, amikacin, phenobarbital, perindopril) using renal function status markers; and the impact of drug interactions on the distribution and elimination of phenobarbital. The thesis summarizes original papers on these topics. Individual pharmacokinetic parameters were calculated for each patient based on their demographic and clinical characteristics, dosing records and measured serum drug levels. The relationships between distribution volume/drug clearance and body size descriptors/renal functional status markers were examined by regression analysis. Vancomycin volume of distribution was best predicted by the total body weight. Loading dose of 10.7 mg/kg of total body weight was optimal in patients taking continuous vancomycin and would lead to reducing of median time to reach target concentrations from 17 to 1 hour. On the contrary, amikacin volume of distribution was most associated...
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Customer satisfaction with offer of services of golf courses in Prague and in Liberec region
Šíma, Martin ; Čáslavová, Eva (advisor) ; Ruda, Tomáš (referee)
Title: Customer satisfaction with offer of services of golf courses in Prague and in Liberec region Objectives: The Diploma Thesis aims to make a survey of satisfaction and expectations of golf course customers in Liberec region and in the capital city Prague and to compare those regions. Customer satisfaction will be measured by means of questionnaires where each player of each golf course will compare real perceived qualities of a golf course with generally expected qualities. Based on the data obtained, the analysis of values will be carried on, such as golf handicap, age, gender and month income. The Thesis will focus on comparing the expectations and satisfaction of major golf resorts with smaller and not so popular ones. Methods: The research of customer satisfaction was carried on by already proven questionnaire consisting of SERVQUAL method. The research compared expected quality with real quality in seven golf courses in Prague and surroundings and in seven golf courses in Liberec region. The research was carried on from August 2014 till February 2015. Results: The outcome of the thesis is to learn about satisfaction of golfers at golf courses in Prague and Liberec region and submit proposals for improving each golf courses in an effort to achieve improved and better access to customers....
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