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Important factors for pharmacokinetics of cyclosporine A in children with kidney transplant

dc.contributor.advisorKostić, Mirjana
dc.contributor.otherLežaić, Višnja
dc.contributor.otherNaumović, Radomir
dc.contributor.otherŽivković, Maja
dc.creatorCvetković, Mirjana Z.
dc.date.accessioned2019-01-25T15:28:06Z
dc.date.available2019-01-25T15:28:06Z
dc.date.issued2018-07-18
dc.identifier.urihttp://eteze.bg.ac.rs/application/showtheses?thesesId=6521
dc.identifier.urihttps://fedorabg.bg.ac.rs/fedora/get/o:19276/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70036&RID=50757647
dc.identifier.urihttp://nardus.mpn.gov.rs/123456789/10660
dc.description.abstractTransplantacija bubrega je najpoželjniji metod lečenja pedijatrijskih pacijenata sa terminalnom bubrežnom insuficijencijom, a Ciklosporin A (CsA) je imunosupresivni lek koji se koristi kod transplantiranih bolesnika u cilju prevencije odbacivanja kalema. Različita ekspresija komponenata familije enzima CYP3A (prvenstveno CYP3A4 i CYP3A5), POR enzima i P-glikoproteina može biti uzrok individualne varijabilnosti u apsorpciji, metabolizmu i tkivnoj distribuciji CsA. Individualni odgovor na terapiju može biti uslovljen prisustvom različitih alelnih varijanti (polimorfizama tipa zamene jednog nukleotidnog ponovka , eng. single nucleotide polymorphisms-SNP) u genima koji kodiraju navedene enzime i transporter. Takođe, biološko sazrevanje dečijeg organizma doprinosi razlikama u farmakokinetici CsA u grupi pedijatrijskih pacijenata. Ciljevi studije: 1. da se utvrdi frekvencija alela i genotipova polimorfizama u genima za ABCB1 (rs1045642), CYP3A5 (rs776746), CYP3A4 (rs35599367) i POR (rs1057868) kod pedijatriskih pacijenata sa transplantiranim bubregom u Srbiji, 2. da se ispita uticaj uzrasta pacijenta, kao nezavisnog faktora, na farmakokinetiku CsA tokom prve godine nakon transplantacije, 3. da se ispita uticaj polimorfizama u genima za ABCB1 (rs1045642), CYP3A5 (rs776746), CYP3A4 (rs35599367) i POR (rs1057868) na farmakokinetiku CsA kod pedijatrijskih pacijenata sa transplantiranim bubregom u Srbiji, tokom prve godine nakon transplantacije, 4. da se ispita uticaj polimorfizama u genima za ABCB1 (rs1045642), CYP3A5 (rs776746), CYP3A4 (rs35599367) i POR (rs1057868) u zavisnosti od uzrasta pacijenta, na farmakokinetiku CsA kod pedijatrijskih pacijenata sa transplantiranim bubregom u Srbiji, tokom prve godine nakon transplantacije. Metodologija: Istraživanje je obavljeno na Univerzitetskoj dečjoj klinici, u Centru za hemodijalizu i transplantaciju, jedinom mestu u Srbiji, gde se radi transplantacija bubrega kod pedijatrisjkih pacijenata uz njihovo postransplantaciono praćenje. U studiju je uključeno 47 pacijenata kojima je transplantiran bubreg u periodu od 2001-2015 godine. Pacijentima je nakon transplantacije uključen CsA u terapiju...sr
dc.description.abstractKidney transplantation is the most desirable method for the treatment of children with terminal renal insufficiency and Cyclosporine A (CsA) is a cornerstone of immunosuppressive therapy used in transplanted patients, in order to prevent the rejection of kidney. Different expression of components of the CYP3A enzyme family (primarily CYP3A4 and CYP3A5), POR enzyme and of P-glycoprotein, may be the cause of individual variability in absorption, metabolism and tissue distribution of CsA. Individual response to therapy may be conditioned by the presence of various allelic variants (single nucleotide polymorphisms-SNP) in genes encoding said enzymes and a transporter. Also, biological maturation of child organism contributes to differences in the pharmacokinetics of CsA in a group of pediatric patients. Aim: 1.to determine the frequency of alleles and genotypes of polymorphisms in genes for ABCB1 (rs1045642), CYP3A5 (rs776746), CYP3A4 (rs35599367) and POR (rs1057868) in children with kidney transplants in Serbia; 2. to investigate the effect of polymorphisms in the genes of ABCB1 (rs1045642), CYP3A5 (rs776746), CYP3A4 (rs35599367) and POR (rs1057868) on the pharmacokinetics of CsA in children with kidney transplants in Serbia; 3. to consider the influence of child age as an independent factor on the pharmacokinetics of CsA in children with kidney transplants in Serbia; 4. to investigate the effect of polymorphisms in the genes of ABCB1 (rs1045642), CYP3A5 (rs776746), CYP3A4 (rs35599367) and POR (rs1057868) on the age of the patient, on the pharmacokinetics of CsA in children with kidney transplants in Serbia. Methodology: The research was carried out at the University Children's Hospital, at the Center for Hemodialysis and Transplantation, the only place in Serbia, where kidney transplants are performed, in line with post-transplant monitoring. The study included 47 children who had a kidney transplant in the period of 2001-2015. Patients received CsA in the after transplantation treatment. Regular controls were performed 1, 3, 6 and 12 months after the transplantation and whenever needed by the doctor's assessment...en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Београду, Медицински факултетsr
dc.rightsAutorstvo-Nekomercijalno-Bez prerade 3.0 Srbija (CC BY-NC-ND 3.0)
dc.sourceУниверзитет у Београдуsr
dc.subjectdeca, uzrast, transplantacija bubrega, Ciklosporin A, polimorfizamsr
dc.subjectchildren, age, kidney transplantation, Cyclosporine A , polymorphismen
dc.titleFaktori od značaja za farmakokinetiku ciklosporina A kod dece sa transplantiranim bubregomsr
dc.title.alternativeImportant factors for pharmacokinetics of cyclosporine A in children with kidney transplanten
dc.typePhD thesis


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