Specialer
Bente Steffansen
Lektor
E-mail: bds(at)farma.ku.dk
Telefon: 35 33 62 21
Rum: 13/421
Interactions on membrane transporters: experimental approach
The bioavailability of many drug substances/excipients may be mediated or compromised by one or several membrane transporters. For example is the absorption of many statin drugs influenced by absorptive and exsorptive transporters. The goal of the project is to investigate drug-drug/drug-excipient interactions on membrane transporters by studying in vitro permeability of the compounds in play. The experimental strategy is to use cell cultures expressing several membrane transporters, such as the Caco-2 cells, and investigate how drug substances/excipients interactions on transporters may influence permeability of probe (biomarker) substrates.
Supervisor Bente Steffansen and possibly a PhD student
Interactions on membrane transporters: regulatory affairs
The bioavailability of many drug substances/excipients may be mediated or compromised by one or several membrane transporters giving rise to possible interaction between drug substances/excipients on the transporters. Thus, the US Food and Drug Administration (FDA) as well as the European Medicines Agency (EMA) have submitted guidelines, regarding interaction studies on transporters, to guide companies in how to identify possible clinical relevant interactions on transporters by in vitro studies performed in the preclinical phase of development.
The goal of the project is to compare the guidelines. Furthermore to critically evaluate the suitability of the suggested in vitro studies described in the guidelines, i.e. suitability to identify clinical relevant drug-drug interactions on transporters in the preclinical phase of development.
Supervisors Bente Steffansen and possible co-supervisor from the Danish Medicines Agency
Characterisation of interaction between platinum-based drugs and cell membrane transporters
Cisplatin is one of the most widely used anticancer drugs but the applicability of the drug is limited to a relative narrow range of tumor types. Numerous platinum-based drug candidates have been examined with the purpose to minimize side effects and avoid drug resistance. The aim of this project is to improve our knowledge on the resistance mechanism of platinum compounds using selected platinum drug compounds in an in vitro model. The strategy is to use Caco-2 cell cultures as a model for the cancer cells and use competition assays to investigate the role of absorptive/exorptive membrane transporters in development of drug resistance.
Supervisors: Bente Gammelgaard and Bente Steffansen
Glycoside prodrugs: synthesis, in vitro metabolism and permeability studies.
Some glycosides are substrates to glucose transporter SGLT. This transporter is responsible for the absorption of glucose across the small intestine. SGLT is expressed in DMTZ-Caco-2 cells and the permeability of glucose as well as the glycoside piceid is mediated by SGLT in these cells. By means to enhance solubility and obtain a good permeability of the compound Licochalcon A the goal of the project is to synthesize glycoside prodrugs of Licochalcon A, followed by studies of the prodrugs aqueous solubility as well as SGLT mediated permeability across DMTZ-Caco-2 cells.
Supervisors: Bente Steffansen & Søren Brøgger Christensen
Earlier Masters projects;
Master thesis’ , carried out under the supervision of Bente Steffansen, are available upon request.
External Masters projects;
Some collaboration with industry or academic partners may be possible upon request.
