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Forschungsverbünde deutscher Hochschulen auf dem Gebiet der Klinischen Pharmazie [FoKP2-I]
Klinische Pharmazie, das jüngste der fünf pharmazeutischen Kernfächer, ist nach wie vor nicht an allen Hochschulstandorten durch einen forschenden Arbeitskreis vertreten. Dennoch sind die Forschungsprojekte im Fach Klinische Pharmazie meist sehr interdisziplinär angelegt und die Partner zu größeren Verbünden zusammengeschlossen. Ziel der Arbeit ist, 17 Jahre nach Eingang des Fachs Klinische Pharmazie in die Approbationsordnung für Apotheker und 4 Jahre nach der ersten im AK Kloft durchgeführten bundesweiten Erhebung zu größeren Forschungskooperationen/Forschungsverbünden im Fach Klinische Pharmazie, eine erneute Bilanz zur Forschungsaktivität des Faches zu ziehen. Veränderungen und Entwicklungen im Vergleich zur letzten Erhebung sollen zusammengetragen und damit der wissenschaftliche Beitrag des Faches neu bewertet werden. Nach Abschluss der Pilotphase sollen in der Hauptphase die Untersuchung mittels online-Fragebogen durchgeführt und ggf., je nach zeitlicher Kapazität, die gewonnenen Daten ausgewertet werden.
Weitere Informationen: FoKP2-I
Literature research: Translation of in vitro and animal studies for nebulized (protein) drugs and drugs with pulmonary action [FAIR-TRANS]
Bacterial pneumonia is a leading cause of morbidity and mortality worldwide, currently treated with antibiotics. This standard of care faces antimicrobial resistance (AMR) and thus curative failure. Other treatment options currently being investigated are the use of immunomodulatory proteins derived from bacteria, which enhance airway epithelial innate immune defences and increases the therapeutic outcome relative to antibiotic alone. The safety, efficacy and PK/PD of these compounds is first investigated in vitro and in animals before the translation to man is made.
In this project, previous translational work regarding nebulized drugs or drugs with pulmonary action will be collected and summarized in order to provide a state of the art approach for new compounds.
Further information: FAIR-TRANS
Literature research: Association between neutrophil: Lymphocyte ratio and treatment outcome in lung cancer [NLR]
Lung cancer is the leading killer among cancers worldwide. Combination chemotherapy e.g. paclitaxel plus cisplatin or carboplatin is the only treatment option in advanced disease stages (stage III/IV), however treated patients show poor prognosis, with less than 5% of the patients surviving >5 years. Markers such as disease stage, patient performance status and even gender have been evaluated as predictors of treatment outcome, but these do not perform well in advanced disease. The ratio of neutrophils to lymphocytes (neutrophil:lymphocyte ratio) before start or during chemotherapy at specific time points have been shown to be a good predictor of treatment outcome in various cancers (lung cancer inclusive). In this work, you will perform literature research from online resources to summarise studies that evaluated neutrophil:lymphocyte ratio as a predictor on treatment outcome in non-small cell lung cancer focusing on studies in which paclitaxel, carboplatin or cisplatin was one of the administered drugs.
Further information: NLR
Literature research: Nebulization of protein drugs and its effect on pharmacokinetics and pharmacodynamics [FAIR-NEB]
Bacterial pneumonia is a leading cause of morbidity and mortality worldwide, currently treated with antibiotics. This standard of care faces antimicrobial resistance (AMR) and thus curative failure. Other treatment options currently being investigated are the use of immunomodulatory proteins derived from bacteria, which enhance airway epithelial innate immune defences and increases the therapeutic outcome relative to antibiotic alone. In this project, the nebulization modalities for optimal airway targeting and rapid action at the infection site of proteins are investigated. In order to develop a pulmonary (inhalation) dose, knowledge about the influence of nebulization on protein characteristics is of utmost importance.
Further information: FAIR-NEB
Literature research: Combinatorial therapies for non-small cell lung carcinoma with sensitizing mutations of the epithelial growth factor receptor: Mechanisms of resistance and overcoming them [EGFR]
Non-small cell lung cancer is the most common type of lung cancer, amounting to almost 85% of lung carcinomas. Many (40-80%) of these are associated with overexpression of the epithelial growth factor receptor (EGFR), of which a subpopulation is treatable with EGFR-binding tyrosine kinase inhibitors such as Erlotinib. However, after initial treatment success, resistance often occurs due to a variety of mechanisms such as mutation or downregulation of the receptor. Combination therapy with other inhibitors offer an attractive solution for this resistance, as a large interaction signalling network (interactome) is associated with the EGFR and other pathways might thus be upregulated during resistance.
Further information: EGFR
Literature research: Renal replacement therapy in patients and how to adapt drug dosing [PIP-RRT]
Renal replacement therapies are used to filter the blood of patients facing renal failure due to an acute kidney injury or chronic kidney diseases. In the clinic various types of renal replacement therapies are used and they all effect the elimination processes of drugs given to the patients. The magnitude of this effect is depending on the type of renal replacement therapy, the extend of the renal impairment and the given drug.
Weitere Informationen: PIP-RRT
Literaturgestützter Vergleich der analysemethoden klinischer Mikrodialysedaten [INF_µD]
Microdialysis is a minimally invasive method to obtain drug concentrations at target site in virtually any tissue. However, analysis of such data is not trivial and there is no consensus on what methodology to employ. In a systematic review of available literature the aims of this analysis are:
Overview of clinical studies including the microdialysis technique categorised by the employed analysis method.
Comparison of outcomes with respect to pharmacokinetic parameters and their variability between the different analysis approaches.
Weitere Informationen: INF_µD
Literature Research: Physiologically based pharmacokinetic modelling of Infiximab in bowel diseases. [INFLIX]
Over the past few decades, monoclonal antibodies (mAbs) have become one of the most important and fastest growing classes of therapeutic molecules, with applications in a wide variety of disease areas such inflammatory bowel diseases (IBD). However, their pharmacological (pharmacokinetic and pharmacodynamic) properties differ substantially from small molecule drugs. In this context, physiologically-based pharmacokinetic (PBPK) models are an interesting approach to characterise the different pharmacokinetic processes of these mAbs. Here, we will focus on infliximab, an anti-TNFα mAb indicated in the treatment of patients with moderate to severe IBD.
Further information: INFLIX
Effect of liver transplantation on CYP3A activity [LIVER]
Cytochrome P450 plays an important role in the metabolism of several drugs. The most abundant isoform is CYP3A which is responsible for the metabolism of more than 50% of drugs. CYP3A is mainly present in the liver and intestine. Like with other enzymes, hepatic CYP3A activity is greatly affected by the physiological status of the liver e.g. hepatic circulation, presence/absence of inflammation, aging, etc. Liver damage and the necessity of liver transplantation is of no exception. The project aims to identify the changes in hepatic CYP3A activity encountered as a result of the latter procedure. Will extrahepatic CYP3A become overexpressed and take over? Will the lag time between liver transplant and restoration of blood flow affect the restored hepatic CYP3A activity? A case example, from the literature, on one of the CYP3A substrates’ fate before and after liver transplant is also encouraged.
Further information: LIVER
Role of Biomarkers (Carcinoembryonic antigen (CEA) and cytokeratin-19 fragments (CYFRA 21-1) in non-small cell lung cancer (NSCLC) [Biomark]
Non-small cell lung cancer (NSCLC) accounts for approximately 85% of all lung cancer cases. Early diagnosis is usually difficult due to the absence of clinical symptoms. In addition, monitoring response has been restricted to imaging techniques that hardly capture unmeasurable disease. Therefore, more surrogate measures are needed for both diagnosis and disease/treatment monitoring. Biomarkers, among which carcinoembryonic antigen (CEA) and cytokeratin-19 fragments(CYFRA21-1), have been potential surrogates with increasing and debatable interpretations on their screening, diagnostic, monitoring, predictive and prognostic capabilities.
This project aims to assess the various potential roles of both CEA and CYFRA21-1 in NSCLC through an extensive literature review with emphasis on areas with greatest potential for future research.
Further information: BIOMARK
Literature Research: Pharmacokinetic/pharmacodynamic of Anti-TNF (focus on Infiximab) in inflammatory bowel diseases [Anti-TNF]
Therapeutic monoclonal antibodies (mAbs) against the cytokine TNFα are a standard treatment for patients with moderate to severe inflammatory bowel diseases (IBD). The understanding of the pharmacokinetic/pharmacodynamic (PK/PD) relationship of those compounds is essential to adapt the dosing regimen to the patients and optimise therapy.
Further information: Anti-TNF
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