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Design of Pilot Clinical Trial of Treatment of Hepatitis C in Polyvalent Problem Drug Users with Pharmacological Substitution of Opioids and Methamphetamine (HCV-PPDUSOM)
Oktábec, Zbyněk ; Gabrhelík, Roman (advisor) ; Minařík, Jakub (referee)
Charles University in Prague First Faculty of Medicine Study programme: Specialization in Health Care Branch of Study: Addictology PharmDr. Bc. Zbyněk Oktábec, Ph.D. et Ph.D. Design of Pilot Clinical Trial of Treatment of Hepatitis C in Polyvalent Problem Drug Users with Pharmacological Substitution of Opioids and Methamphetamine (HCV-PPDUSOM) Master's Thesis Advisor: Mgr. Roman Gabrhelík, Ph.D. Prague, 2016 Abstract Hepatitis C is one of the most serious blood-borne complications of somatic health status of drug users. The HCV-positive injecting drug users are therefore directly indicated for the treatment of this type (and other types also) of hepatitis. Problematic adherence and treatment compliance is obvious in this group. Both foreign and domestic experiences show that stabilization of the use of illegal (and/or illegally acquired) substances is the essential part of the treatment of hepatitis. The interaction of the high quality treatment of somatic, psychosocial and add-on pharmacological care, including the substitution of illegal (and/or illegally acquired) drugs, leads to patient's increased compliance and adherence to HCV treatment. This diploma thesis is presenting both the theoretical frame and the study design of the pilot clinical trial of HCV treatment with the supportive substitution...
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Study of Interactions between API and Excipients in Solid Drug Formulation
Oktábec, Zbyněk ; Vinšová, Jarmila (advisor) ; Pekárek, Tomáš (referee)
CHARLES UNIVERSITY IN PRAGUE PHARMACEUTICAL FACULTY IN HRADEC KRÁLOVÉ DEPARTMENT OF ANORGANIC AND ORGANIC CHEMISTRY Rigorous Thesis Study of interactions between API and excipients in solid drug formulation Mgr. Zbyněk Oktábec A drug formulation usually consists of an active pharmaceutical ingredient(s) - API(s) - combined with excipients that have been added to the formulation: 1. to facilitate its preparation 2. to ensure the required stability of the drug in the formulation during the manufacturing process 3. during the storage 4. to function as a drug delivery system 5. many others The interactions in formulations can influence pharmaceutical and biopharmaceutical properties, such as physical and chemical stability, dissolution rate, and total bioavailability, of the final dosage form. This thesis dealt with the preparation of binary mixtures of API and excipients and their analyses. The preparation of binary mixtures was in correlation with formulation process. The following analyses proceeds by Fourier transform near-infrared spectroscopy (FT-NIR), which is a fast andnon-destructive analytical technique that offers many advantages for a broad range of applications. Main topic was to observe the possible interaction of API and excipients and/or to describe the polymorphism of the API,...
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Recent Findings on the Pharmacotherapy of Methamphetamine Dependence: Potentially Suitable Substances for Methamphetamine Substitution
Oktábec, Zbyněk ; Gabrhelík, Roman (advisor) ; Minařík, Jakub (referee)
Charles University in Prague First Faculty of Medicine Study programme: Specialization in Health Care Branch of Study: Addictology PharmDr. Zbyněk Oktábec, Ph.D. et Ph.D. Recent Findings on the Pharmacotherapy of Methamphetamine Dependence: Potentially Suitable Substances for Methamphetamine Substitution Bachelor's Thesis Advisor: Mgr. Roman Gabrhelík, Ph.D. Prague, 2014 Abstract Methamphetamine has long been a lead drug of abuse among problem drug users on the Czech drug scene. At the moment, there is no worldwide effective pharmacological treatment of addiction on the methamphetamine/amphetamine-like substances. There have been found substances, with the greater or lesser success, from different ATC groups as well as some new substances, which some patients/clients could profit from. Nevertheless we still fail to find a widely effective pharmacotherapy of methamphetamine dependence, which would be efficacious and broadly applicable, i.e. as the substances in the treatment of opioid dependence. This work aims to present current information on substitution and/or craving reduction therapy in the treatment of methamphetamine dependence. This paper has the character of a research/review work and uses up-to-date data, not only in published articles and in the primary literature, but in ongoing clinical trials...
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Design of Pilot Clinical Trial of Treatment of Hepatitis C in Polyvalent Problem Drug Users with Pharmacological Substitution of Opioids and Methamphetamine (HCV-PPDUSOM)
Oktábec, Zbyněk ; Gabrhelík, Roman (advisor) ; Minařík, Jakub (referee)
Charles University in Prague First Faculty of Medicine Study programme: Specialization in Health Care Branch of Study: Addictology PharmDr. Bc. Zbyněk Oktábec, Ph.D. et Ph.D. Design of Pilot Clinical Trial of Treatment of Hepatitis C in Polyvalent Problem Drug Users with Pharmacological Substitution of Opioids and Methamphetamine (HCV-PPDUSOM) Master's Thesis Advisor: Mgr. Roman Gabrhelík, Ph.D. Prague, 2016 Abstract Hepatitis C is one of the most serious blood-borne complications of somatic health status of drug users. The HCV-positive injecting drug users are therefore directly indicated for the treatment of this type (and other types also) of hepatitis. Problematic adherence and treatment compliance is obvious in this group. Both foreign and domestic experiences show that stabilization of the use of illegal (and/or illegally acquired) substances is the essential part of the treatment of hepatitis. The interaction of the high quality treatment of somatic, psychosocial and add-on pharmacological care, including the substitution of illegal (and/or illegally acquired) drugs, leads to patient's increased compliance and adherence to HCV treatment. This diploma thesis is presenting both the theoretical frame and the study design of the pilot clinical trial of HCV treatment with the supportive substitution...
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PHARMACOTERAPEUTIC INTERVENTIONS IN ADDICTION TREATMENT
Kozinski, Jan ; Minařík, Jakub (advisor) ; Oktábec, Zbyněk (referee)
Drug dependence is one of the most common psychiatric diagnosis besides with affective disorders and anxiety disorders. Drug abuse may entail many somatic and psychiatric comorbidities which complicate treatment and substantially worsen its prognosis. Allthough the main reason of keeping dependence behaviour are maladaptive behavioural patterns, on the cell level there are mainly pathophysiological processes in the central nervous systém. Similarly, it can be supposed that centre of treatment lies in psychotherapy, nevertheless parallel medication may significantly reduce subjective difficulties connected with abstinence from drug, which are common reason from treatment terminating from the side of patient. In the urgent addictology, or acute psychiatry it is possible to meet with situations, when psychotherapeutic techniques have only limited effectiveness. It is possible to use for example de-escalate approach with anxious patient that is intoxicated by cannabinoids or halucinogens, but it has no efficacy in the case of life-threatening acute intoxication by anticholinergics, opioids or tranquillisers. Similarly, in the case of acute withdrawal syndrome after long abuse of drugs with strong physical dependence, such as alcohol or benzodiazepines may physician almost exclusively rely on...
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Recent Findings on the Pharmacotherapy of Methamphetamine Dependence: Potentially Suitable Substances for Methamphetamine Substitution
Oktábec, Zbyněk ; Gabrhelík, Roman (advisor) ; Minařík, Jakub (referee)
Charles University in Prague First Faculty of Medicine Study programme: Specialization in Health Care Branch of Study: Addictology PharmDr. Zbyněk Oktábec, Ph.D. et Ph.D. Recent Findings on the Pharmacotherapy of Methamphetamine Dependence: Potentially Suitable Substances for Methamphetamine Substitution Bachelor's Thesis Advisor: Mgr. Roman Gabrhelík, Ph.D. Prague, 2014 Abstract Methamphetamine has long been a lead drug of abuse among problem drug users on the Czech drug scene. At the moment, there is no worldwide effective pharmacological treatment of addiction on the methamphetamine/amphetamine-like substances. There have been found substances, with the greater or lesser success, from different ATC groups as well as some new substances, which some patients/clients could profit from. Nevertheless we still fail to find a widely effective pharmacotherapy of methamphetamine dependence, which would be efficacious and broadly applicable, i.e. as the substances in the treatment of opioid dependence. This work aims to present current information on substitution and/or craving reduction therapy in the treatment of methamphetamine dependence. This paper has the character of a research/review work and uses up-to-date data, not only in published articles and in the primary literature, but in ongoing clinical trials...
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Modification of Physico-Chemical Properties of Biologically Active Compounds
Oktábec, Zbyněk ; Vinšová, Jarmila (advisor) ; Matějka, Pavel (referee) ; Kratochvíl, Bohumil (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Inorganic and Organic Chemistry Candidate PharmDr. Zbyněk Oktábec Supervisor prof. RNDr. Jarmila Vinšová, CSc. Title of Thesis Modification of Physico-Chemical Properties of Biologically Active Compounds The majority of newly developed biologically active compounds (API) belong to the 2. - 4. BCS class, i.e. groups that have problematic permeability and/or solubility. This work deals with modifications of the physico-chemical properties of model biologically active substances. The first group selected for these modifications were bisphosphonates - ibandronate and risedronate. By using a rational selection of co-crystallisation partners, co-crystals of model APIs were prepared with co-crystallisation partners from the group of monosaccharides and their derivatives. Available solid state analytical methods - NIR, Raman spectroscopy, 31 P CP/MAS NMR - were used for the characterization of the resulting cocrystal(s), and in the case of co-crystals of risedronate salt, 13 C CP/MAS NMR, XRPD and DSC were used. There was only one positive sample among all the prepared samples of co-crystals of ibandronate salt, and that was with the use of phenyl-β-D- galactopyranoside as a co-crystallisation partner. PAMPA experiments were...
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Synthesis of antimicrobial active anilides and their sulphur analogues
Oktábec, Zbyněk ; Vinšová, Jarmila (advisor) ; Macháček, Miloš (referee)
CHARLES UNIVERSITY IN PRAGUE PHARMACEUTICAL FACULTY IN HRADEC KRÁLOVÉ DEPARTMENT OF ANORGANIC AND ORGANIC CHEMISTRY Diploma Thesis Synthesis Of Antimicrobial Active Anilides and Their Sulphur Analogues Zbyněk Oktábec Implementation of tert-butyl group into the molecule of benzoxazoles leads to enhancement of lipophility and therefore better penetration through lipoid mycobacterial cell-wall. Several derivates had shown 100-90 % activity in concentration 6,25 μg/ml against Mycobacterium tuberculosis H37Rv in our series of 5,7-di-tert-butyl-benzoxazoles substituted in position No. 2 with aromatic substituent. Metabolism of benzoxazoles probably includes the opening of their structure. The goal of this thesis is to synthesize substituted N-(3,5-di-tert-butyl-2-hydroxyphenyl)benzamides and pyridinecarboxamides, their so-called "open forms". These structures could be also considered as "reversed salicylanilides" which have also a significant antitubercular activity. The first step of the synthesis of these analogues is preparation of 2-amino-3,5-di-tert- butylphenol. It was prepared by reaction of 3,5-di-tert-butylbenzo-1,2-quinone with ammonia and following reduction by NaBH4. Resulting DTB-aminophenol has been condensed with appropriate aromatic or heteroaromatic acids, while PCl3 in chlorobenzene was...
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Study of Interactions between API and Excipients in Solid Drug Formulation
Oktábec, Zbyněk ; Vinšová, Jarmila (advisor) ; Pekárek, Tomáš (referee)
CHARLES UNIVERSITY IN PRAGUE PHARMACEUTICAL FACULTY IN HRADEC KRÁLOVÉ DEPARTMENT OF ANORGANIC AND ORGANIC CHEMISTRY Rigorous Thesis Study of interactions between API and excipients in solid drug formulation Mgr. Zbyněk Oktábec A drug formulation usually consists of an active pharmaceutical ingredient(s) - API(s) - combined with excipients that have been added to the formulation: 1. to facilitate its preparation 2. to ensure the required stability of the drug in the formulation during the manufacturing process 3. during the storage 4. to function as a drug delivery system 5. many others The interactions in formulations can influence pharmaceutical and biopharmaceutical properties, such as physical and chemical stability, dissolution rate, and total bioavailability, of the final dosage form. This thesis dealt with the preparation of binary mixtures of API and excipients and their analyses. The preparation of binary mixtures was in correlation with formulation process. The following analyses proceeds by Fourier transform near-infrared spectroscopy (FT-NIR), which is a fast andnon-destructive analytical technique that offers many advantages for a broad range of applications. Main topic was to observe the possible interaction of API and excipients and/or to describe the polymorphism of the API,...
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