Primjena kromatografskih tehnika za predviđanje apsorpcije febuksostata

master's thesis

• Title (english): Application of chromatographic technique to predict absorption of febuxostat
• Author: Vedrana Golek
• Mentor: Ana Mornar Turk (mentor)
• Committee member: Ana Mornar Turk (predsjednik povjerenstva)
• Committee member: Biljana Nigović (član povjerenstva)
• Committee member: Sandra Jurić (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of pharmaceutical analysis); Zagreb
• Defense date and country: 2016-09-27, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Karakteristike idealnog lijeka su selektivno biološko djelovanje, bez nuspojava i toksičnosti. Da bi se to postiglo,
potrebno je dobro definirati željeni učinak lijeka te odgovarajućim metodama ispitati posjeduje li lijek specifično
djelovanje te kolika mu je učinkovitost i selektivnost djelovanja.
Definiranje poželjnih fizikalno-kemijskih parametara u ranim fazama istraživanja lijekova smanjuje pojavu neželjenih
spojeva u daljnjim koracima istraživanja. Pored eksperimentalnih ispitivanja, u zadnje vrijeme sve češće se u ranim
fazama istraživanja lijekova primjenjuje in silico postupci.
Fizikalno-kemijski parametar lipofilnosti je iznimno važan stručnjacima koji istražuju nove lijekove, farmakolozima,
analitičarima, farmaceutskim tehnolozima i drugim istraživačima iz područja farmaceutske znanosti. Ono utječe na
transport lijeka kroz stanične membrane, interakciju lijeka s transportnim proteinima, aktivnost i metabolizam lijeka,
odnosno na njegovu farmakokinetiku i farmakodinamiku.
Nove spoznaje o fizikalno-kemijskim parametrima bioraspoloživosti febuksostata omogućile bi bolje razumijevanje
njihove biološke učinkovitosti. Kao dobar izbor promatranja su se pokazale kromatografske tehnike, posebno
tekućinska kromatografija visoke djelotvornosti s umjetnim membranama koje daju vjerniji uvid u rezultate s in vivo
uvjetima.
Ovim radom je provedena kromatografija visoke djelotvornosti s vezanim umjetnim membranama na primjeru lijeka
febuksostata koji se koristi u terapiji hiperuricemije. Korištene su kolone s vezanim fosfolipidnim membranama kako
bi se stvorili uvjeti slični biološkim te predvidjela bolja permeabilnost lijeka. Umjetne membrane ne predviđaju samo
lipofilnost lijekova, nego upućuju i na stupanj interakcije sa fosfolipidima. Febuksostat se pokazao kao lipofilan lijek
koji stupa u interakcije sa fosfolipidima, odnosno upućuje da prelazi kroz staničnu membranu. Nadalje, primjenom
računalnog programa pkCSM in silico postupcima ispitano je njegovo farmakokinetičko ponašanje.

Abstract (english)

Characteristics of an ideal drug are perfectly selective biological activity, without the side effects and toxicity. For
achieving that, it needs to a well define desired effect of the drug and appropriate methods to examine if it has a
specific activity of this drug and how much is the efficacy and selectivity of action.
Defining the desirable physical and chemical parameters in the early stages of drug research suppresses the formation
of unwanted compounds in the further steps of research. Optimization of conditions is simple with the help of highthroughput technology and recently the introduction of in silico.
Physico-chemical parameters of lipophilicity is the basis of observation by experts who investigate new drugs and
pharmacologists, analysts, pharmaceutical technologists and other experts in the field of pharmaceutical sciences. It
affects the transport of drugs through cell membranes, the interaction with the drug transport proteins, the activity and
metabolism of the drug or its pharmacokinetics and pharmacodynamics.
New insights into the physical and chemical parameters bioavailability febuxostat would allow a better understanding
of their biological efficiency. As good choice of observations have been shown as chromatographic techniques,
especially high-performance liquid chromatography with an immobilised artificial membrane which give the faithful
insight into the results from the in vivo conditions.
This work was carried out by HPLC with the immobilised artificial membrane for febuxostat drug that is used in the
treatment of hyperuricemia. Columns, with bounded phospholipid membranes to create conditions similar to
biological and predict better permeability of the drug, were used. Artificial membranes not only predict lipophilicity of
drugs, but also point to the degree of interaction with phospholipids. The obtained results have shown that febuxostat
is a lipophilic drug that interacts with the phospholipids or suggesting that passes through the cell membrane.
Furthermore, the ADME parameters of febuxostat were investigated by using in silico approach.

• Keywords: febuksostat; farmakokinetika; ADME; bioraspoloživost; lipofilnost; IAM-HPLC; QSRR
• Keywords (english): febuxostat; pharmacokinetics; ADME; bioavailability; lipophilicity; IAM-HPLC; QSRR
• Language: croatian
• URN:NBN: urn:nbn:hr:163:749492
• 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: Access restricted to students and staff of home institution
• Created on: 2016-12-08 14:52:51