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dc.creatorGolubović, Bojana
dc.creatorVučićević, Katarina
dc.creatorRadivojević, Dragana
dc.creatorVezmar-Kovačević, Sandra
dc.creatorProstran, Milica
dc.creatorMiljković, Branislava
dc.date.accessioned2019-09-02T12:11:03Z
dc.date.available2019-09-02T12:11:03Z
dc.date.issued2019
dc.identifier.issn1452-8258
dc.identifier.urihttp://farfar.pharmacy.bg.ac.rs/handle/123456789/3340
dc.description.abstractBackground: Due to wide intra- and inter-individual pharmacokinetic variability and narrow therapeutic index of sirolimus, the therapeutic drug monitoring (TDM) of sirolimus with detailed biochemical and clinical monitoring is necessary for dose individualization in kidney transplant patients. The purpose of the study was to explore and identify factors that contribute to pharmacokinetic variability by developing and validating a population model using routine TDM data and routinely monitored biochemical and clinical parameters. Methods: The data obtained by routine monitoring of 38 patients over a period of one year from the sirolimus treatment initiation, were collected from patients' records. Population analysis was performed using the software NONMEM (R). The validity of the model was tested by the internal and external validation techniques. Results: The pharmacokinetic variability was partially explained with patient's age and liver function. CL/F was found to decrease with age. According to the developed model, sirolimus CL/F decreases by, in average, 37% in patients with aspartate aminotransferase (AST) greater than 37 IU/L. The internal and external validation confirmed the satisfactory prediction of the developed model. Conclusions: The population modeling of routinely monitored data allowed quantification of the age and liver function influence on sirolimus CL/F. According to the final model, patients with compromised liver function expressed via AST values require careful monitoring and dosing adjustments. Proven good predictive performance makes this model a useful tool in everyday clinical practice.en
dc.publisherDruštvo medicinskih biohemičara Srbije, Beograd i Versita
dc.relationinfo:eu-repo/grantAgreement/MESTD/Basic Research (BR or ON)/175023/RS//
dc.rightsopenAccess
dc.sourceJournal of Medical Biochemistry
dc.subjectaspartate aminotransferaseen
dc.subjectkidney transplantationen
dc.subjectpharmacokineticsen
dc.subjectsirolimusen
dc.subjecttherapeutic drug monitoringen
dc.titleExploring sirolimus pharmacokinetic variability using data available from the routine clinical care of renal transplant patients-population pharmacokinetic approachen
dc.typearticle
dc.rights.licenseARR
dcterms.abstractВезмар-Ковачевић, Сандра; Радивојевић, Драгана; Миљковић, Бранислава; Простран, Милица; Голубовић, Бојана; Вучићевић, Катарина;
dc.citation.volume38
dc.citation.issue3
dc.citation.spage323
dc.citation.epage331
dc.citation.other38(3): 323-331
dc.citation.rankM23
dc.identifier.wos000468363100010
dc.identifier.doi10.2478/jomb-2018-0030
dc.identifier.pmid31156343
dc.identifier.scopus2-s2.0-85056191771
dc.identifier.fulltexthttp://farfar.pharmacy.bg.ac.rs//bitstream/id/1904/3338.pdf
dc.identifier.rcubconv_4381
dc.type.versionpublishedVersion


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