Farmakogenetika inhibitora protonske pumpe

professional thesis

• Author: Martina Vlašić
• Mentor: Nada Božina (mentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Nada Božina (član povjerenstva)
• Committee member: Vesna Bačić Vrca (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2022-03-10, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Cilj istraživanja: Cilj ovog rada je utvrditi utjecaj genetičkog polimorfizma CYP2C19 na farmakokinetiku inhibitora protonske pumpe (IPP) te prikazati utjecaj različitih varijanti ovog gena na ishode liječenja.
Materijali i metode: Pretraživanjem znanstvene literature detaljno je opisan utjecaj polimorfizma CYP2C19 na IPP-e i ishode liječenja ovisno o fenotipu. Pretraživanjem terapijskih smjernica stručnih farmakogenomskih društava, pregledno su prikazane preporuke o prilagodbi farmakoterapije farmakogenomskim analizama.
Rezultati: Polimorfizam gena CYP2C19 utječe na farmakoterapiju s IPP-ima. Fenotip sporog i intermedijarnog metabolizatora povezuje se s boljim terapijskim ishodom u odnosu na normalne, brze i ultra brze metabolizatore. Zbog povišene razine IPP-a u serumu ti pacijenti kod kronične terapije mogu razviti više nuspojava. Primjena IPP-a s drugim lijekovima - supstratima, inhibitorima ili induktorima enzima CYP2C19 - dovodi do različitog terapijskog ishoda ovisno o fenotipu.
Zaključak: Doziranje IPP-a prema genotipu CYP2C19 može pomoći u individualizaciji farmakoterapije s IPP-ima i boljem terapijskom ishodu.

Abstract (english)

Objectives: The aim of this study was to determine the influence of CYP2C19 genetic polymorphism on the pharmacokinetics of proton pump inhibitors (PPI) and to show the influence of different variants of this gene on treatment outcomes.
Materials and methods: By reviewing scientific literature the effect of CYP2C19 polymorphism on PPI and phenotype-dependent treatment outcomes was described in detail. By searching through therapeutic guidelines of professional pharmacogenomic societies the recommendations on the adaptation of pharmacotherapy to pharmacogenomic analyzes were clearly presented.
Results: Polymorphism of the CYP2C19 gene affects pharmacotherapy with PPIs. The slow and intermediate metabolizer phenotype is associated with a better therapeutic outcome compared to normal, fast and ultrafast metabolizers. Due to elevated serum PPI levels these patients may develop more side effects with chronic therapy. Administration of PPIs with other drugs, substrates, inhibitors or inducers of CYP2C19 enzymes leads to a different therapeutic outcome depending on the phenotype.
Conclusion: Dosing of PPIs according to the CYP2C19 genotype may help to individualize pharmacotherapy with PPIs and improve the therapeutic outcome.

• Keywords: CYP2C19; farmakoterapija; inhibitor protonske pumpe; IPP
• Keywords (english): CYP2C19; pharmacotherapy; proton pump inhibitors; PPI
• Language: croatian
• URN:NBN: urn:nbn:hr:163:731666
• Study programme: Title: Clinical pharmacy; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni/a magistar/sveučilišna magistra kliničke farmacije (sveučilišni/a magistar/sveučilišna magistra kliničke farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2022-03-15 11:39:58