Terapijsko praćenje serumske koncentracije biološkog lijeka infliksimaba

master's thesis

• Title (english): Therapeutic drug monitoring of serum concentrations of infliximab
• Author: Ana Pocrnja
• Mentor: Nada Vrkić (mentor)
• Committee member: Nada Vrkić (predsjednik povjerenstva)
• Committee member: Olga Gornik (član povjerenstva)
• Committee member: Marija Grdić Rajković (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; (Department of medical biochemistry and haematology); Zagreb
• Defense date and country: 2016-07-13, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Medical Biochemistry

Abstract

Infliksimab je protuupalni lijek, odnosno kimerno monoklonsko protutijelo subklase IgG1κ, koje se visokim afinitetom veže za topljivi i za membranu vezani čimbenik nekroze tumora alfa te na taj način blokira vezanje TNF-α na receptor i ispoljavanje njegovog proupalnog učinka. Spada u skupinu bioloških lijekova. Primjenjuje se kod bolesnika s kroničnim upalnim bolestima crijeva, kože i reumatskim bolestima. Ciljne terapijske koncentracije lijeka iznose 3-7 μg/mL. Cilj ovog istraživanja je utvrditi koncentracije infliksimaba kod bolesnika s kroničnim upalnim bolestima u ovisnosti o vremenu od započinjanja terapije te utvrditi stupanj povezanosti između doze i koncentracije infliksimaba u odnosu na klinički odgovor pacijenta na terapiju. U ovo prospektivno istraživanje uključena su 23 bolesnika koja boluju od kroničnih crijevnih upalnih bolesti i reumatoidnog artritisa te su na terapiji infliksimabom. Za 23 bolesnika zaprimljena su 42 uzorka seruma (za 19 bolesnika uzorkovalo se prije dviju uzastopnih doza). Srednja koncentracija infliksimaba iznosila je 4,6 (1,1-12,2) μg/mL. Nije pronađena korelacija između doze i koncentracije lijeka (r=-0,14; P=0,40), dok je pronađena negativna korelacija između koncentracije lijeka i tjedna od početne terapije (r=-0,57; P<0,001). U inicijalnoj fazi liječenja (0-14. tjedan) koncentracija infliksimaba bila je statistički značajno viša 14,2 (6,5-20,1) μg/mL) nego u postignutoj ravnoteži (nakon 14. tjedna) (2,47 (0,9-6,9) μg/mL; P<0,001). Za pouzdanu interpretaciju terapijske koncentracije infliksimaba korisno je određivati razinu nakon inicijalne faze, odnosno nakon 14. tjedna kad se dosegne ravnotežna koncentracija lijeka.

Abstract (english)

Infliximab is an anti-inflammatory drug or a chimeric monoclonal antibody of the IgG1κ subclass, which binds with high affinity to the soluble and membrane-bound form of tumor necrosis factor α and thus prevents TNF-α from binding to its receptor and its anti-inflammatory effect. It belongs to a group of biologic drugs. It is used in patients with chronic inflammatory bowel diseases, skin and rheumatic diseases. Targeting therapeutic drug concentrations are of 3-7 μg / mL. The purpose of the study is to determine the concentrations of infliximab in patients with chronic inflammatory diseases, depending on the time of the therapy start and the degree of correlation between the dose of and the concentration of infliximab in relation to the patient's clinical response to therapy. 23 patients were included in this prospective study. The 42 serum samples were collected from the 23 patients (for 19 patients samples were collected before dosing). The mean infliximab concentration was 4.6 (1.1 to 12.2) μg / mL. No correlation was found between the drug dose and the drug concentration (r = -0.14; p = 0.40), while negative correlation was found between the drug concentration and the week from the therapy start (r = -0.57; p <0.001). For patients in the initial phase of treatment (0-14 weeks) the concentration of infliximab was significantly higher (14.2 (6.5 to 20.1) μg / mL) than in patients who achieved state of remission (after 14th week) (2.47 (0.9 to 6.9) μg / mL; p <0.001). In conclusion , for reliable interpretation of therapeutic concentrations of infliximab is useful to determine the level after the initial phase , ie after 14th weeks when it reaches the equilibrium concentration of the drug.

• Keywords: infliksimab; biološka terapija; imunosupresivi; kronične upalne bolesti
• Keywords (english): infliximab; biologic therapy; immunosuppressants; chronic inflammatory diseases
• Language: croatian
• URN:NBN: urn:nbn:hr:163:108284
• Study programme: Title: Medical biochemistry; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: magistar/magistra medicinske biokemije (magistar/magistra medicinske biokemije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Access restricted to students and staff of home institution
• Created on: 2016-12-07 10:26:05