Interactions of antiretrovirals with drug efflux transporters and their role in the transplacental pharmacokinetics

Charles University in Prague, Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Mgr. Zuzana Ptáčková Supervisor: prof. PharmDr. František Štaud, Ph.D. Consultant: PharmDr. Lukáš Červený, Ph.D. Title of doctoral thesis: Interactions of antiretrovirals with drug efflux transporters and their role in the transplacental pharmacokinetics The combination antiretroviral therapy that should be administered during the whole pregnancy is the backbone of prevention of mother-to-child transmission of HIV infection. One of the prophylactic mechanisms of such treatment is the presence of antiretrovirals in the fetal circulation. However this can be associated with the potentially harmful effects of drugs on the developing fetus. To select optimal therapy while minimizing risks it is inevitable to have detailed knowledge of all the factors affecting transplacental transport of drugs. The aim of this study was to detect whether drug efflux transporters are able to protect fetus against xenobiotics can affect the transplacental pharmacokinetics of the selected antiretroviral drugs. Employing variety of in vitro, in vivo, in situ and ex vivo methods we determined the role of the drug efflux transporters in the distribution of drugs between mother and fetus. We suggested that..