Study on interaction potential of maraviroc with drug transporters ABCB1 and ABCG2

Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Kateřina Erbenová Supervisor: PharmDr. Martina Čečková, Ph.D. Title of diploma thesis: Study of interactions antiretroviral drug maraviroc with drug transporters ABCB1 and ABCG2. Maraviroc is inhibitor of CCR5 HIV virus entry into the cells representing one of the important components of antiretroviral therapy. To optimize the treatment strategies and minimize the therapeutic risks of maraviroc-containing combination antiretroviral therapy, it is important to know the interactions of this drug with other antiretrovirals. In particular, interaction on membrane transporters may affect pharmacokinetics and thereby the tissue concentrations of administered drugs, leading to insufficient efficacy of the therapy or increased toxicity. The aim of this study was to experimentally evaluate interaction of maraviroc with the two most important active drug transporters of the ABC transporter superfamily, ABCB1 (P-glycoprotein) and ABCG2 (BCRP). Using in vitro methods employing cell lines we aimed to fulfil two main goals: (1) to evaluate the inhibitory effect of maraviroc on ABCB1 and ABCG2 transporters and (2) to study if any of these transporters could transfer maraviroc as their substrate. The data..