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National Repository of Grey Literature 2 records found  Search took 0.01 seconds. 
Interaction studies of MEK inhibitors and Cytochrome P450 3A4
 Urban, Michal ; Pávek, Petr (advisor) ; Nová, Alice (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Mgr. Michal Urban Supervisor: Doc. PharmDr. Petr Pávek, Ph.D. Title of rigorous thesis: Interaction studies of MEK inhibitors and Cytochrome P450 3A4 Objective of our work was to introduce a new method for detection of CYP3A4 inhibition effect of potentially therapeutical compounds. CYP3A4 is the main biotransformation enzyme of 50% current drugs in clinical use and its inhibition may lead to the plasma levels increase of other coadministered drugs which may result in various drug- drug interactions and potentially life threatening adverse effects. Potential of a drug candidate to cause severe pharmacokinetic interactions may be a reason of the clinical trials suspension or withdrawal of a medicinal product from the market and therefore it is essential to determine pharmacokinetic profile of drug candidates at early stages of the development. In addition, we focused on study of interaction potential of MEK1/2 inhibitors PD0325901, PD184352 and U0126 known to inhibit Ras/Raf/MEK/ERK pathway playing an important role in the oncogenesis of various malignancies. Due to the fact that some of these MEK1/2 inhibitors have already entered clinical trials it is absolutely crucial to study...
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Drug Interactions with Nuclear Receptors in the Regulation of Drug Metabolizing Enzymes and Drug Transporters
 Nová, Alice ; Pávek, Petr (advisor) ; Skálová, Lenka (referee) ; Souček, Pavel (referee)
Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department: Pharmacology and Toxicology Candidate: Alice Nová, MSc Supervisor: Assoc. Prof. PharmDr. Petr pávek, Ph.D. Title of Doctoral Thesis: Drug interactions with nuclear receptors in the regulation of drug metabolizing enzymes and drug transporters Drug metabolizing enzymes play a key role in metabolism, elimination and detoxification of xenobiotics exposed to the body and protect the organism from potentially harmful effect of xenobiotics as well as certain endobiotics. Phase I and II drug metabolizing enzymes and drug transporters are expressed in most tissues in basal level or may be induced after exposure to xenobiotics. Affecting of expression or activity of drug metabolizing enzymes and drug transporters may result in unpredictable tissue and systemic drug distribution, to side effects or therapy failure. Up-regulation of drug metabolizing enzymes and drug transporters mediates mainly orphan nuclear receptors - pregnane X receptor (PXR) and constitutive androstane receptor (CAR) and transcription factor aryl hydrocarbon receptor (AhR). This doctoral thesis presents the results of three studies dealing with the gene regulation of drug metabolizing enzymes and drug transporters via nuclear receptors. In the first part of...
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See also: similar author names
1 NOVÁ, Adéla
9 NOVÁ, Alena
2 NOVÁ, Andrea
9 Nová, Alena
2 Nová, Andrea
4 Nová, Aneta
1 Nová, Anna
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