Prikaz osnovnih podataka o disertaciji
Meta-analiza podataka o razlikama u izloženosti psihijatrijskim lekovima između sporih i normalnih CYP2C19/CYP2D6 metabolizera
Meta-analysis of the data on differences in the exposure to psychiatric drugs between poor and normal cYP2C19/CYP2D6 metabolizers
dc.contributor.advisor | Jukić, Marin | |
dc.contributor.other | Pešić, Vesna | |
dc.contributor.other | Stanić, Dušanka | |
dc.contributor.other | Miljević, Čedo | |
dc.contributor.other | Starčević, Ana | |
dc.creator | Milosavljević, Filip | |
dc.date.accessioned | 2023-05-18T12:56:10Z | |
dc.date.available | 2023-05-18T12:56:10Z | |
dc.date.issued | 2022-10-21 | |
dc.identifier.uri | https://eteze.bg.ac.rs/application/showtheses?thesesId=9082 | |
dc.identifier.uri | https://fedorabg.bg.ac.rs/fedora/get/o:29312/bdef:Content/download | |
dc.identifier.uri | https://plus.cobiss.net/cobiss/sr/sr/bib/80769289 | |
dc.identifier.uri | https://nardus.mpn.gov.rs/handle/123456789/21427 | |
dc.description.abstract | Postoji mogućnost da genetski predodređene razlike između osoba u kapacitetu CYP450 enzima mogu uticati na farmakoterapiju u psihijatriji. Cilj ovog istraživanja bio je precizna kvantifikacije uticaja CYP2C19/CYP2D6 fenotipa na izloženost antidepresivima i antipsihoticima metodom meta-analize odnosa srednjih vrednosti. Drugi cilj bio je ispitivanje uticaja CYP2C19 fenotipa na efikasnost i podnošljivost antidepresiva pomoću kliničke studije u kojoj su hospitalizovani pacijenti praćeni četiri nedelje. Serija meta-analiza podataka iz 94 jedinstvene studije na ukupno 8379 precizno je kvantifikovala povećanu izloženost escitalopramu (+163%; 95%CI: +140%, 189%; n=1262, p<0,0001) i sertralinu (+38%; 95%CI: +27%, +51%; n=917, p<0,0001) kod osoba sa genetski predviđenim smanjenim kapacitetom CYP2C19 enzima, kao i povećanu izloženost risperidonu (+36%; 95%CI: +28%, +44%; n=1492, p<0,0001), aripiprazolu (+48%; 95%CI: +41%, +57%; n=1038, p<0,0001) i haloperidolu (+68%; CI95%: 40%, 102%; n=423, p<0.0001) kod osoba sa genetski predviđenim smanjenim kapacitetom CYP2D6 enzima. Klinička studija demonstrirala je da su, u toku četiri nedelje, osobe sa sporijim CYP2C19 metabolizmom imale 36% (95%CI: 20-52%, p<0,0001) manje izraženo poboljšanje simptoma depresije (praćeno Hamilton skalom za depresiju) i značajno veći intenzitet neželjenih efekata vezanih za gastrointestinalni (q=0,002) i centralni nervni sistem (q=0,045) što je mereno Toronto skalom, u odnosu na kontrolne osobe. Zbog visoke preciznosti kvantifikacije, rezultati meta-analiza mogu poslužiti kao osnova za kliničke smernice za precizno doziranje ispitivanih lekova na osnovu CYP2C19/CYP2D6 genotipa. Takođe, rezultati kliničke studije naglašavaju da CYP2C19 genotip može biti klinički važna informacija u psihijatrijskoj praksi. | sr |
dc.description.abstract | Genetically predicted interindividual differences in activites of CYP450 enzymes may significantly influence pharmacotherapy in psychiatry. The aim of this research was to precisely quantify the influence of CYP2C19/CYP2D6 phenotype on the exposure to antidepressants and antipsychotics with ratio-of-means meta-analysis. Other aim was to determine the influence of CYP2C19 phenotype on the efficacy and tolerability of antidepressants in the clinical study of inpatients that were monitored for four weeks. Meta-analyses of the data from 94 unique studies and 8379 participants precisely quantified the increased exposure to escitalopram (+163%; 95%CI: +140%, 189%; n=1262, p<0.0001) and sertraline (+38%; 95%CI: +27%, +51%; n=917, p<0.0001) in participants with genetically predicted decreased CYP2C19 capacity; and increased exposure to risperidon (+36%; 95%CI: +28%, +44%; n=1492, p<0.0001), aripiprazole (+48%; 95%CI: +41%, +57%; n=1038, p<0.0001) and haloperidol (+68%; CI95%: 40%, 102%; n=423, p<0.0001) in participants with genetically predicted decreased CYP2D6 enzyme capacity. Clinical study revealed that, during 4 weeks, patients with decreased CYP2C19 activity had 36% (95%CI: 20-52%, p<0.0001) less pronounced depression symptom improvement (monitored with Hamilton depression rating scale), and significantly higher intensity of central nervous system (q=0.002) and gastrointestinal (q=0.042) adverse reactions (monitored with Toronto adverse reaction scale), compared to controls. Due to high quantification precision, results of the meta-analyses may serve as a basis for precise dosing guidelines, for examined drugs, that are based on CYP2C19/CYP2D6 genotype. Also, clinical study results suggest that CYP2C19 genotype may be useful clinical information in psychiatric practice. | en |
dc.format | application/pdf | |
dc.language | sr | |
dc.publisher | Универзитет у Београду, Фармацеутски факултет | sr |
dc.rights | openAccess | en |
dc.rights.uri | https://creativecommons.org/licenses/by-nc/4.0/ | |
dc.source | Универзитет у Београду | sr |
dc.subject | Antidepresivi | sr |
dc.subject | Antidepressants | en |
dc.subject | Antipsychotics | en |
dc.subject | CYP2C19 | en |
dc.subject | CYP2D6 | en |
dc.subject | Pharmacogenetics | en |
dc.subject | Precise medicine | en |
dc.subject | Meta-analysis | en |
dc.subject | Clinical study | en |
dc.subject | Antipsihotici | sr |
dc.subject | CYP2C19 | sr |
dc.subject | CYP2D6 | sr |
dc.subject | Farmakogenetika | sr |
dc.subject | Precizna medicina | sr |
dc.subject | Meta-analiza | sr |
dc.subject | Klinička studija | sr |
dc.title | Meta-analiza podataka o razlikama u izloženosti psihijatrijskim lekovima između sporih i normalnih CYP2C19/CYP2D6 metabolizera | sr |
dc.title.alternative | Meta-analysis of the data on differences in the exposure to psychiatric drugs between poor and normal cYP2C19/CYP2D6 metabolizers | en |
dc.type | doctoralThesis | |
dc.rights.license | BY-NC | |
dc.identifier.fulltext | http://nardus.mpn.gov.rs/bitstream/id/150922/Disertacija_13522.pdf | |
dc.identifier.fulltext | http://nardus.mpn.gov.rs/bitstream/id/152750/Referat.pdf | |
dc.identifier.rcub | https://hdl.handle.net/21.15107/rcub_nardus_21427 |