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The influence of individual genetic predisposition to the pharmacokinetics and pharmacodynamics of chosen opioids
Matoušková, Olga ; Perlík, František (advisor) ; Votava, Martin (referee) ; Mičuda, Stanislav (referee)
MUDr. Olga Matoušková - the dissertation theses The influence of individual genetic predisposition to the pharmacokinetics and pharmacodynamics of chosen opioids ABSTRACT Introduction: The aim of this thesis is to study the influence of polymorphism of CYP2D6 and MDR1 on the pharmacokinetics and pharmacodynamics of tramadol in healthy volunteers using measurement. A secondary objective is to evaluate these polymorphisms in relation to the analgesic efficacy and side effects of piritramide for acute postoperative pain. Materials and methods: In two prospective work studying the influence of genetic predisposition on the pharmacokinetic and pharmacodynamic parameters of tramadol, we included a total of 90 healthy volunteers. Clinical studies on opioid analgesia and influence of genetic predisposition to the pharmaco-therapeutic effects and side effects in patients with acute postoperative pain, we included a total of 161 patients with acute postoperative pain. Polymorphism genotyping CYP2D6 and MDR1 gene we performed PCR - RFLP analysis, to determine concentrations of tramadol and metabolite, we used gas and liquid chromatography and pharmacodynamic effects of opioids was evaluated by pupilometric measurement and visual analogue scale. Results and conclusion: Variability of the opioid effect is influenced by...
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Applications of chiral and achiral chromatography in pharmacology and toxicology
Chytil, Lukáš ; Slanař, Ondřej (advisor) ; Bultas, Jan (referee) ; Coufal, Pavel (referee)
Development and validation of methods for analysis of several drugs or their metabolites are decribed in this thesis. The document is presented as a commentary to the original papers, which were published in peer reviewed journals. Discussion on the optimization of each method is presented and covers also method development and influence of preanalytical aspects. Additionally, examples of the application of the developed methods in clinical pharmacology and toxicology are shown. This dissertation consists of three parts: enantiomeric determination of tramadol and its metabolite, determination of some antihypertensive drugs, and qualitative analysis of benzodiazepines. Development of a method for chiral analysis of tramadol and its desmethylated metabolite O- desmethyltramadol (ODT) in human urine and plasma is described in the first part of the thesis. Tramadol is a centrally acting analgetic drug, which is used as racemate in clinical practise. Each enantiomer displays different binding properties for various receptors: (+)-tramadol preferentially inhibits serotonin reuptake while (-)-tramadol mainly inhibits noradrenalin reuptake. (+)-tramadol is considered 10-times more potent than (-)-tramadol. Major active metabolite (ODT), which is considered to be the main agent responsible for the...
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The influence of individual genetic predisposition to the pharmacokinetics and pharmacodynamics of chosen opioids
Matoušková, Olga ; Perlík, František (advisor) ; Votava, Martin (referee) ; Mičuda, Stanislav (referee)
MUDr. Olga Matoušková - the dissertation theses The influence of individual genetic predisposition to the pharmacokinetics and pharmacodynamics of chosen opioids ABSTRACT Introduction: The aim of this thesis is to study the influence of polymorphism of CYP2D6 and MDR1 on the pharmacokinetics and pharmacodynamics of tramadol in healthy volunteers using measurement. A secondary objective is to evaluate these polymorphisms in relation to the analgesic efficacy and side effects of piritramide for acute postoperative pain. Materials and methods: In two prospective work studying the influence of genetic predisposition on the pharmacokinetic and pharmacodynamic parameters of tramadol, we included a total of 90 healthy volunteers. Clinical studies on opioid analgesia and influence of genetic predisposition to the pharmaco-therapeutic effects and side effects in patients with acute postoperative pain, we included a total of 161 patients with acute postoperative pain. Polymorphism genotyping CYP2D6 and MDR1 gene we performed PCR - RFLP analysis, to determine concentrations of tramadol and metabolite, we used gas and liquid chromatography and pharmacodynamic effects of opioids was evaluated by pupilometric measurement and visual analogue scale. Results and conclusion: Variability of the opioid effect is influenced by...
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Applications of chiral and achiral chromatography in pharmacology and toxicology
Chytil, Lukáš ; Slanař, Ondřej (advisor) ; Bultas, Jan (referee) ; Coufal, Pavel (referee)
Development and validation of methods for analysis of several drugs or their metabolites are decribed in this thesis. The document is presented as a commentary to the original papers, which were published in peer reviewed journals. Discussion on the optimization of each method is presented and covers also method development and influence of preanalytical aspects. Additionally, examples of the application of the developed methods in clinical pharmacology and toxicology are shown. This dissertation consists of three parts: enantiomeric determination of tramadol and its metabolite, determination of some antihypertensive drugs, and qualitative analysis of benzodiazepines. Development of a method for chiral analysis of tramadol and its desmethylated metabolite O- desmethyltramadol (ODT) in human urine and plasma is described in the first part of the thesis. Tramadol is a centrally acting analgetic drug, which is used as racemate in clinical practise. Each enantiomer displays different binding properties for various receptors: (+)-tramadol preferentially inhibits serotonin reuptake while (-)-tramadol mainly inhibits noradrenalin reuptake. (+)-tramadol is considered 10-times more potent than (-)-tramadol. Major active metabolite (ODT), which is considered to be the main agent responsible for the...
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