Trenutno važeći EU standard dokaza terapijske ekvivalencije generičkih proizvoda mikofenolat mofetila

master's thesis

• Title (english): Currently valid EU standards of assessing therapeutic equivalence of generic products of mycophenolate mofetil
• Author: Hrvoje Brajčić
• Mentor: Vladimir Trkulja (mentor)
• Committee member: Vlasta Bradamante (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: VLADIMIR TRKULJA (član povjerenstva)
• Granter: University of Zagreb; School of Medicine; (Department of Pharmacology); Zagreb
• Defense date and country: 2014-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Basic Medical Sciences; Pharmacology

Abstract

Mikofenolat mofetil, prolijek mikofenolne kiseline je imunosupresivni lijek koji je postao obvezatnidio terapije u posttransplantacijskih bolesnika i u nekim autoimunim bolestima. Površina ispod krivulje (AUC) mikofenolne kiseline je u direktnoj svezi s uspješnim ishodom terapije i ima zamjetnu intraindividualnu i interindividualnu varijabilnost pri primjeni peroralnog pripravka u obliku mikofenolat mofetila i samim time zahtjeva konstantno praćenje i titraciju. Nadalje, mikofenolat mofetil ulazi u interakcije s lijekovima koji utječu na probavni sustav i interakciju s hranom. Krovna agencija za odobravanje lijekova u EU; EMA trenutno traži za dokazivanje bioekvivalencije generika mikofenolat mofetila samo jednu studiju u uvjetima gladovanja dok FDA; krovna agencija u SAD-u traži uz studiju u uvjetima gladovanja i studiju nakon jela. Pretraživanjem elektronske baze podataka PubMed Medline pronađeno je 16 radova (na temu fizikalno-kemijska i biofarmaceutska svojstva MMF-a, apsorpcija MMF-a iz probavnog sustava u ljudi ili životinja, klinička djelotvornost generičkih formulacija MMF-a) od kojih je 14 bilo moguće nabaviti u punom izdanju. Dobiveni radovi ne daju konačan odgovor na pitanje, ali potvrđuju sumnju da postoji izrazita mogućnost da po trenutnim EMA standardima za dokazivanje bioekvivalencije generičkih proizvoda mikofenolat mofetila oni nisu nužno terapijski ekvivalenti originalnom proizvodu u realnom okruženju.

Abstract (english)

Mycophenolate mofetil, mycophenolic acid's prodrug is an imunosuppressive drug, which has become a mandatory part of therapy in posttransplantation patients and in some autoimmune diseases. Area under curve (AUC) of mycophenolic acid is in direct connection with successful therapy outcome and has a noticeable interindividual and intraindividual variability when peroral mycophenolate mofetil is used and thus requires a constant surveillance and titration. Furthermore, in several papers an interaction was described of mycophenolate mofetil and other drugs which influence the digestive system and interaction with food. The European Medicines Agency, EMA, currently requires for assessing bioequivalence of generic products of mycophenolate mofetil only a single bioequivalence study in fasting state, while FDA; requires a study in the fasting state and another one in the fed state. While searching through PubMed Medline 16 papers have been found (concerning physiochemical and biopharmaceutical properties of MMF, absorption of MMF from digestive system in humans and animals, clinical effectiveness of generic products of MMF) of which 14 were available in full text. These papers do not give a final answer to the question, but confirm the doubt that there is a significant possibility that current EMA standards for assessing bioequivalence of generic products of mycophenolate mofetil might not guarantee therapeutic equivalence of generics in the real-life environment.

• Keywords: mikofenolat mofetil; mikofenolna kiselina; bioekvivalencija; generički pripravci; EMA standardi bioekvivalencije
• Keywords (english): mycophenolate mofetil; mycophenolic acid; bioequivalence; generic products; EMA standards of bioequivalence
• Language: croatian
• URN:NBN: urn:nbn:hr:105:048995
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2015-09-16 12:20:03