@conference{
author = "Škorić, Biljana and Jovanović, Marija and Miljković, Branislava and Kuzmanović, Miloš and Vučićević, Katarina",
year = "2022",
abstract = "Administration of high dose methotrexate (HDMTX) is common part of pediatric
protocols for acute lymphoblastic leukemia (ALL) and non-Hodking lymphoma (NHL).
Methotrexate is used in certain phase of therapy in doses 3 g/m 2 or 5 g/m 2 with the objective
to achieve concentration that will ensure eradication of tumor cells with minimal toxic effect.
The aim of this study is overview of drug concentration and assessment of therapy safety in
relation to referent values. After obtaining Ethics committee approval at The Institute for
mother and child Healthcare of Serbia “Dr Vukan Cupic” 50 pediatric patients with ALL or
NHL were enrolled. Data on MTX usage was retrospectively collected from the patient
history. Concentrations and normalized concentrations per applied dose were compared
with nonparametric tests in SPSS (version 18). MTX concentration mean (± standard
deviation) following administration of 3 g/m 2 respectively 5 g/m2 doses were 19.72±6.62
mg/L respectively 34.73±17.13 at 24 h, 0.20±0.36 mg/L respectively 0.24±0.58 mg/L at 48h
and 0.14±0.44 mg/L respectively 0.12±0.89 mg/L at 72h after start of the infusion.
Statistically significant difference (p<0.001) is only seen at 24h concentration between 3
g/m 2 (mean rank 43.97) and 5 g/m 2 (mean rank 103.36). In all other time points, there was
no difference during comparison of concentrations nor normalized concentration, even
though it is seen trend of higher values in 5 g/m2 group. Results of analysis show that
administration of higher dose during simultaneous distribution and elimination phase leads
to higher concentrations while during elimination phase this effect is less visible. However,
administration of the high doses brings the risk of side effects due to reaching higher
concentrations., Primena visokih doza metotreksata je uobičajena u pedijatrijskim protokolima za
lečenje akutne limfoblastne leukemije (ALL) i non-Hodking limfoma (NHL). Metotreksat se u
određenoj fazi terapije primenje u dozi od 3 g/m2 ili 5 g/m 2 u cilju postizanja koncentracije
koje uništavaju tumorske ćelije uz minimalan toksičan efekat. Cilj ovog rada je prikaz
koncentracije leka u zavisnosti od primenjene doze i procena bezbednosti terapije u odnosu
na referentne vrednosti koncentracije. Nakon odobrenja etičkog odbora Instituta za
zdravstvenu zaštitu majke i deteta Srbije „Dr Vukan Čupić“ uključeno je 50 pedijatrijski
pacijenata sa ALL ili NHL. Podaci o primeni MTX su retrospektivno prikupljeni iz istorija
bolesti. Koncentracije i normalizovane koncentracije po primenjenoj dozi su statistički
analizirani neparametarskim testovima u SPSS-u (verzija 18). Srednja vrednost
koncentracija (± standardna devijacija) MTX pri primeni 3 g/m2 odnosno 5 g/m2 je iznosila
19,72±6,62 mg/L odnosno 34,73±17,13 u 24h, 0,20±0,36 mg/L odnosno 0,24±0,58 mg/L u
48h i 0,14±0,44 mg/L odnosno 0,12±0,89 mg/L u 72h posle početka infuzije. Statistički
značajna razlika (p<0,001) je uočena kod koncentracija u 24h između doza 3 g/m2 (mean
rank = 43,97) i 5 g/m2 (mean rank= 103,36). U ostalim vremenskim tačkama i pri poređenju
normalizovanih koncentracija nije bilo statistički značajne razlike, iako je primetan trend
viših vrednosti u grupi 5 g/m 2 . Rezultati analize pokazuju da pri primeni veće doze leka
tokom istovremene distribucije i eliminacije leka postoji mogućnost detektovanja visokih
koncentracija, dok je tokom faze eliminacije uticaj primenjene doze manje uočljiv. Ipak,
primena veće doze nosi rizik od neželjenih efekata.",
publisher = "Savez farmaceutskih udruženja Srbije (SFUS)",
journal = "Arhiv za farmaciju",
title = "Assessment of concentrations and normalized concentrations of variability in methotrexate concentrations between cycles, Ispitivanje koncentracija i normalizovanih koncentracija metotreksata u zavisnosti od primenjene doze u pedijatrijskoj populaciji sa ALL i NHL",
volume = "72",
number = "4 suplement",
pages = "S290-S291",
url = "https://hdl.handle.net/21.15107/rcub_farfar_4529"
}
