Farmakogenetika antidepresiva

master's thesis

• Title (english): Pharmacogenetics of antidepressants
• Author: Lino Nikolić
• Mentor: Karmela Barišić (mentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Lidija Bach-Rojecky (član povjerenstva)
• Committee member: Iva Mucalo (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of biochemistry and molecular biology); Zagreb
• Defense date and country: 2023-07-21, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Farmakogenetika je znanost koja istražuje djelovanje genetskoga profila osobe na učinak lijeka. Antidepresivi su jedna
od najvažnijih skupina lijekova na čiju sudbinu u tijelu u značajnoj mjeri mogu utjecati polimorfizmi gena koji kodiraju
za enzime koji sudjeluju u njihovom metabolizmu (ponajprije riječ je o CYP2D6 i CYP2C19). Geni CYP2D6 i CYP2C19
izrazito su polimorfni te je identificirano 171 odnosno 36 različitih alela.
Cilj diplomskoga rada bio je ustanoviti u kolikoj mjeri i na koji način polimorfizmi gena za različite metaboličke enzime
utječu na sudbinu antidepresiva u organizmu. Rad također donosi pregled dostupnih smjernica za doziranje antidepresiva
po metabolizatorskom statusu (PM, IM, NM, UM). U pisanju diplomskog rada korištene su znanstvene publikacije
objavljene u posljednjih desetak godina u časopisima zastupljenim u: PubMed, ScienceDirect, PharmVar i PharmGKB.
Većinu terapijskih preporuka za doziranje i smjernica izdaje klinički farmakogenetički implementacijski konzorcij
(CPIC). Za primjenu antidepresiva koji su inhibitori ponovne pohrane serotonina (SSRI), poput fluvoksamina, sertralina
i dr., te tricikličkih antidepresiva (TCA), poput amitriptilin, nortriptilin i dr., postoje smjernice formulirane temeljem
rezultata farmakogenetskih/farmakogenomskih istraživanja. Nizozemska farmakogenetička radna skupina (DPWG)
izdaje vlastite smjernice za neke antidepresive poput venlafaksina, amitriptilina i nortriptilina. Polimorfizmi gena za Pgp i 5-HTT mogu u određenoj mjeri utjecati na odgovor pojedinca na antidepresive, no još ne postoje konkluzivna
istraživanja koja bi potvrdila u kolikoj mjeri.
Iz proučavanja prethodno navedene literature može se zaključiti kako je potrebno još neko vrijeme da bi se
farmakogenetika intenzivno implementirala u kliničku praksu, no svakako je prepoznata potreba za njome u budućnosti
personalizirane medicine.

Abstract (english)

Pharmacogenetics is a discipline that deals with determining person's genetic profile and tries to predict best drug in the
optimal dose. Antidepressants are one of the most important drugs that are highly influenced by genetic polymorphisms
in genes that are encoding for enzymes involved in their metabolism (CYP2D6 and CYP2C19 mostly). CYP2D6 and
CYP2C19 are highly polymorphic enzymes of which 171, and 36 respectively, allele variants are known.
The aim of this thesis is to determine how much a certain genetic polymorphism affects the metabolic fate of taken
antidepressant. The thesis also brings an overview of official guidelines for antidepressant dosing based on metabolizer
status (PM, IM, NM, UM). Science articles published in journals in the last decade were found in following databases:
PubMed, ScienceDirect, PharmVar, PharmGKB.
Most of the guidelines are published by Clinical Pharmacogenetics Implementation Consortium (CPIC). SSRIs
(fluvoxamine, sertraline, etc.) and TCAs (amitriptyline, nortriptyline, etc.) are covered by guidelines due to extensive
longterm research. Dutch Pharmacogenetics Working Group (DPWG) also issued its own guidelines for dosing some
antidepressants such as venlafaxine, amitriptyline and nortriptyline. Genetic polimorphisms in enzmyes that encode for
P-gp and 5-HTT can influence an individuals's response to a certain drug, altough there is no conclusive research on this
matter yet.
From studying the aforementioned literature we can conclude that it will take some time till pharmacogenetics can be
fully implemented in clinical practice, but it has been recognised as a future of personalized medicine.

• Keywords: farmakogenetika; CYP2D6; CYP2C19; antidepresivi; polimorfizmi; metabolizatorski status; P-gp
• Keywords (english): pharmacogenetics; CYP2D6; CYP2C19; antidepressants; polymorphisms; metabolizer status; P-gp
• Language: croatian
• URN:NBN: urn:nbn:hr:163:416013
• 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: 2023-11-21 14:58:07