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Pharmacokinetics analysis of tacrolimus in kidney transplant patients

dc.contributor.advisorRadovanović-Veličković, Radmila
dc.contributor.otherMikov, Momir
dc.contributor.otherCvetković, Tatjana,
dc.contributor.otherMitić, Branka
dc.creatorĐorđević-Catić, Aleksandra
dc.date.accessioned2016-01-05T13:22:51Z
dc.date.available2016-01-05T13:22:51Z
dc.date.available2020-07-03T16:08:57Z
dc.date.issued2014-07-04
dc.identifier.urihttp://eteze.ni.ac.rs/application/showtheses?thesesId=950
dc.identifier.urihttp://nardus.mpn.gov.rs/handle/123456789/3928
dc.identifier.urihttps://fedorani.ni.ac.rs/fedora/get/o:807/bdef:Content/download
dc.identifier.urihttp://vbs.rs/scripts/cobiss?command=DISPLAY&base=70052&RID=1024507885
dc.description.abstractTacrolimus (Tac) is an effective immunosuppressive drug that represents a part of standard immunosuppressive protocol for kidney transplant patients. Its leading role in the immunosuppressive therapy is based on the proven benefits in the prevention of acute rejection of transplanted kidney and preservation of graft function. Therapeutic monitoring of Tac and appropriate pharmacokinetic approach are particularly important for optimal immunosuppression due to its interindividual variability and low therapeutic index. It is possible to determine the extent and significance of interindividual variability of Tac by pharmacokinetic analysis. It is known that Tac during the long-term use exerts toxic and adverse effects. It is possible to determine the presence of drug interactions and the correlation between concentration of tacrolimus and its side effects by pharmacokinetic analysis of therapeutic and biochemical monitoring data. The aim of our study was to determine the pharmacokinetic parameters of Tac after the first oral dose and their confirmation in steady state. Non-compartment and population pharmacokinetic analysis of Tac was the basis of the research. Our results showed gender differences in the pharmacokinetics of Tac. Therefore, we conducted selective pharmacokinetic approach after first oral dose of Tac and after achieving steady state. In female patients concentration of Tac two hours after oral administration was determined as an indicator of exposure to tacrolimus after initial oral drug administration and after achieving a steady state. In male patients, three-point method (concentrations of Tac 1, 4 and 12 hours after oral administration), provides a good predictability of the total drug exposure. After reaching a steady state, this method can be replaced by measuring the concentration achieved eight hours after drug administration. During the study it was determined a dose dependence and gender difference of the interaction between corticosteroids and tacrolimus. The results of our study showed that the implementation of therapeutic and biochemical monitoring together enable optimal therapeutic effect with minimizing adverse effects of complex immunosuppressive therapy. It was found by population pharmacokinetic analysis that the effects of corticosteroids on Tac concentration stops with prednisolone daily dose reduction to 25mg. The results of our assessment confirm the necessity for development of pharmacokinetic model of tacrolimus in order to implement a rational pharmacotherapy in renal transplantation patients.en
dc.formatapplication/pdf
dc.languagesr
dc.publisherУниверзитет у Нишу, Медицински факултетsr
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/172044/RS//
dc.rightsopenAccessen
dc.sourceУниверзитет у Нишуsr
dc.subjectTransplantacija bubregasr
dc.titleFarmakokinetička ispitivanja takrolimusa kod pacijenata sa presađenim bubregomsr
dc.titlePharmacokinetics analysis of tacrolimus in kidney transplant patientsen
dc.typedoctoralThesis
dc.rights.licenseBY-NC
dcterms.abstractРадовановић-Величковић, Радмила; Цветковић, Татјана,; Митић, Бранка; Миков, Момир; Ђорђевић-Цатић, Aлександра; Фармакокинетичка испитивања такролимуса код пацијената са пресађеним бубрегом; Фармакокинетичка испитивања такролимуса код пацијената са пресађеним бубрегом;
dc.identifier.fulltexthttp://nardus.mpn.gov.rs/bitstream/id/53734/Disertacija.pdf


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