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Effect of vitamin D on ABCB1 and CYP3A4 expression in human precision-cut intestinal slices
Mazurová, Tereza ; Vokřál, Ivan (advisor) ; Matoušková, Petra (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Student: Tereza Mazurová Supervisor: PharmDr. Ivan Vokřál, Ph.D. Title of diploma thesis: Effect of vitamin D on the expression of ABCB1 and CYP3A4 in human intestinal slices When drugs are administered orally, their absorption is significantly affected by the intestinal barrier. This barrier expresses a variety of efflux and uptake transporters, as well as first and second-phase biotransformation enzymes. The most important efflux transporter in the intestinal barrier is P-glycoprotein, which has a broad substrate specificity. Among the first-phase biotransformation enzymes, cytochrome P450 3A4 is the most important. Their function is to protect the human body from the toxic effects of xenobiotics, including drugs. Many clinically important drugs act as substrates, inhibitors or inducers in relation to these proteins, which may result in an increased risk of drug interactions. A plethora of dietary supplements or medicines containing vitamin D can be found in the pharmacy. It is used for the proper development of bones and teeth, for the proper function of the immune system or for the treatment of osteomalacia, rickets or osteoporosis. Limited information is available on its effects on P-gp and...
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Study of drug-drug interactions of antiviral drugs on intestinal transporters
Záboj, Zdeněk ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Zdeněk Záboj Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Study of drugs interactions of antiviral drugs with intestinal transporters Sofosbuvir is an antiviral agent widely used in the treatment of chronic hepatitis C. This orally administered prodrug is a designed substrate of ATP-binding (ABC) efflux transporters, P- glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). ABCB1 and ABCG2 are important determinants of intestinal absorption and are the site of significant pharmacokinetic drug interactions, leading to changes in drug exposure. Pharmacokinetic drug interactions may be undesirable (increasing the toxicity of the treatment) or desirable (allowing dose reduction). Because sofosbuvir is often administered in combination regimens with other anti(retro)virotics, the aim of this thesis was to study the ability to enhance intestinal absorption of sofosbuvir. To study the pharmacokinetic drug interactions on ABCB1 and ABCG2, a widely established in vitro bi-directional transport method through a polarized monolayer formed by the Caco-2 cell line derived from colorectal cancer has been used. We analyzed the drug interactions of sofosbuvir on these efflux...
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Study of drug-drug interactions of antiviral drugs on intestinal transporters
Záboj, Zdeněk ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Zdeněk Záboj Supervisor: PharmDr. Lukáš Červený, Ph.D. Title of diploma thesis: Study of drugs interactions of antiviral drugs with intestinal transporters Sofosbuvir is an antiviral agent widely used in the treatment of chronic hepatitis C. This orally administered prodrug is a designed substrate of ATP-binding (ABC) efflux transporters, P- glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2). ABCB1 and ABCG2 are important determinants of intestinal absorption and are the site of significant pharmacokinetic drug interactions, leading to changes in drug exposure. Pharmacokinetic drug interactions may be undesirable (increasing the toxicity of the treatment) or desirable (allowing dose reduction). Because sofosbuvir is often administered in combination regimens with other anti(retro)virotics, the aim of this thesis was to study the ability to enhance intestinal absorption of sofosbuvir. To study the pharmacokinetic drug interactions on ABCB1 and ABCG2, a widely established in vitro bi-directional transport method through a polarized monolayer formed by the Caco-2 cell line derived from colorectal cancer has been used. We analyzed the drug interactions of sofosbuvir on these efflux...
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