Provođenje mjera minimizacije rizika primjene fluoropirimidina u Republici Hrvatskoj

master's thesis

• Title (english): Implementation of risk minimization measures for the use of fluoropyrimidines in the Republic of Croatia
• Author: Sara Koren
• Mentor: Nikica Mirošević Skvrce (mentor)
• Mentor: Lana Ganoci (mentor)
• Committee member: Nikica Mirošević Skvrce (predsjednik povjerenstva)
• Committee member: Iva Mucalo (član povjerenstva)
• Committee member: Lana Ganoci (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2023-11-24, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Fluoropirimidini su skupina kemoterapeutika koji se koriste u liječenju više vrsta raka, a uključuju 5-fluorouracil te njegove oralne prolijekove kapecitabin i tegafur.
U metabolizmu fluoropirimidina glavnu ulogu igra enzim dihidropirimidin-dehidrogenaza (DPD) koju kodira gen DPYD. Polimorfizmi i varijante gena DPYD povezuju se s nedostatkom aktivnosti enzima DPD te povećanim rizikom za razvoj teških nuspojava fluoropirimidina. Stoga je objavljeno je više smjernica koje daju preporuke za farmakogenetičko testiranje ovog gena. Cilj testiranja je otkriti moguće varijante gena DPYD prije terapije fluoropirimidinima te smanjiti rizik od nuspojava. Ovaj rad sadrži pregled metoda genotipizacije i fenotipizacije te sažetak najvažnijih nacionalnih smjernica država Europe i Europske agencije za lijekove (EMA).
U sklopu ovog diplomskog rada, obrađeni su podaci farmakogenetičkog testiranja DPYD u pacijenata Republike Hrvatske u periodu od srpnja 2009. do lipnja 2023. godine. Prikazane su statistike o spolu i dobi pacijenata te broju testova provedenih svake godine. Obradom rezultata genotipizacije izračunate su frekvencije pojedinih varijanti u ispitivanoj populaciji te je prikazano podrijetlo preporuka za testiranje na razini primarne, sekundarne i tercijarne zdravstvene zaštite.

Abstract (english)

Fluoropyrimidines are a group of chemotherapeutic drugs used to treat a spectrum of carcinoma. The group includes 5-fluorouracil and its oral prodrugs capecitabine and tegafur.
The enzyme dihydropyrimidine dehydrogenase, coded by the DPYD gene, has a major role in the metabolism of fluoropyrimidines. DPYD polymorphisms and variants are associated with lack of DPD enzyme activity and increased risk for development of fluoropirimidine severe adverse reactions. Therefore, several guidelines for DPYD testing have been published. The goal of these tests is to detect possible variants of the DPYD gene pre-treatment and to minimise the risk of side effects. This paper includes an overview of different genotyping and phenotyping methods, as well as an overview of the most important national guidelines of European countries and the European Medicines Agency (EMA).
In this master's thesis, the results of more than a decade's worth of pharmacogenetic testing of DPYD in patients from the Republic of Croatia are presented. This paper shows the analysis of patients' sex and age and the number of tests performed each year. Included is the calculated frequency of each of the gene variant and the origin of testing recommendations at the primary, secondary and tertiary health care levels.

• Keywords: dihidropirimidin-dehidrogenaza; DPD; DPYD; 5-fluorouracil; 5-FU; kapecitabin; tegafur; genotipizacija
• Keywords (english): dihydropyrimidine-dehydrogenase; DPD; DPYD; 5-fluorouracil; 5-FU; capecitabine; tegafur; genotyping
• Language: croatian
• URN:NBN: urn:nbn:hr:163:385346
• Study programme: Title: Pharmacy; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra farmacije (magistar/magistra farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2024-01-25 14:12:15