High dose methotrexate (MTX) is used in therapy of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients. It acts as competitive inhibitor of dihydrofolate reductase and consequently inhibits synthesis of deoxyribonucleic acid. The bioavailability is dependent upon dose and route of administration. The drug is moderately bound to plasma proteins and distributes in body tissues and cells. After the administration in high doses, MTX partially undergoes hepatic and intracellular metabolism, but renal excretion of parent compound is the main route of elimination. Numerous factors may influence pharmacokinetics and concentration of drug, but primarily the effect of renal function on elimination is described. Delayed elimination might also be the consequence of drug interaction in renal tubules. Toxicity can arise with high MTX doses, especially in patients with delayed MTX elimination. Therapeutic drug monitoring is indicated due to safety... reasons, in order to optimize leucovorin (folinic acid) administration as it reduces MTX toxicity. Considering the variability and the toxicity of high dose MTX therapy, special caution is required in pediatric patients.
Metotreksat (MTX) se u visokim dozama koristi u terapiji akutne limfoblastne leukemije i ne-Hodkinovog limfoma u pedijatrijskoj populaciji. Deluje kao kompetitivni inhibitor dihidrofolat reduktaze i time inhibira sintezu dezoksiribonukleinske kiseline. Stepen biološke raspoloživosti zavisi od puta primene leka i doze. Vezivanje za proteine plazme je u umerenom stepenu, a raspodeljuje se u tkiva i ćelije. Nakon primene u visokim dozama MTX delimično podleže hepatičkom i intracelularnom metabolizmu, ali glavni put eliminacije je preko bubrega u nepromenjenom obliku. Veliki broj faktora utiče na farmakokinetiku i koncentraciju leka, a pre svega je opisan uticaj funkcije bubrega na eliminaciju. Usporena eliminacija može biti i posledica interakcije sa drugim lekovima na nivou transportera u renalnim tubulima. Primena visokih doza MTX nosi rizik od pojave toksičnosti, posebno pri usporenoj eliminaciji. Terapijsko praćenje leka je indikovano iz bezbednosnih razloga, kako bi se optimi...zovala primena leukovorina (folinska kiselina) koji smanjuje toksičnost MTX. Imajući u vidu varijabilnost i toksičnost pri primeni visokih doza MTX poseban oprez je potreban u pedijatrijskoj populaciji pacijenata.
TY - JOUR
AU - Škorić, Biljana
AU - Jovanović, Marija
AU - Miljković, Branislava
AU - Kuzmanović, Marko
AU - Vučićević, Katarina
PY - 2020
UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3596
AB - High dose methotrexate (MTX) is used in therapy of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients. It acts as competitive inhibitor of dihydrofolate reductase and consequently inhibits synthesis of deoxyribonucleic acid. The bioavailability is dependent upon dose and route of administration. The drug is moderately bound to plasma proteins and distributes in body tissues and cells. After the administration in high doses, MTX partially undergoes hepatic and intracellular metabolism, but renal excretion of parent compound is the main route of elimination. Numerous factors may influence pharmacokinetics and concentration of drug, but primarily the effect of renal function on elimination is described. Delayed elimination might also be the consequence of drug interaction in renal tubules. Toxicity can arise with high MTX doses, especially in patients with delayed MTX elimination. Therapeutic drug monitoring is indicated due to safety reasons, in order to optimize leucovorin (folinic acid) administration as it reduces MTX toxicity. Considering the variability and the toxicity of high dose MTX therapy, special caution is required in pediatric patients.
AB - Metotreksat (MTX) se u visokim dozama koristi u terapiji akutne limfoblastne leukemije i ne-Hodkinovog limfoma u pedijatrijskoj populaciji. Deluje kao kompetitivni inhibitor dihidrofolat reduktaze i time inhibira sintezu dezoksiribonukleinske kiseline. Stepen biološke raspoloživosti zavisi od puta primene leka i doze. Vezivanje za proteine plazme je u umerenom stepenu, a raspodeljuje se u tkiva i ćelije. Nakon primene u visokim dozama MTX delimično podleže hepatičkom i intracelularnom metabolizmu, ali glavni put eliminacije je preko bubrega u nepromenjenom obliku. Veliki broj faktora utiče na farmakokinetiku i koncentraciju leka, a pre svega je opisan uticaj funkcije bubrega na eliminaciju. Usporena eliminacija može biti i posledica interakcije sa drugim lekovima na nivou transportera u renalnim tubulima. Primena visokih doza MTX nosi rizik od pojave toksičnosti, posebno pri usporenoj eliminaciji. Terapijsko praćenje leka je indikovano iz bezbednosnih razloga, kako bi se optimizovala primena leukovorina (folinska kiselina) koji smanjuje toksičnost MTX. Imajući u vidu varijabilnost i toksičnost pri primeni visokih doza MTX poseban oprez je potreban u pedijatrijskoj populaciji pacijenata.
PB - Beograd : Savez farmaceutskih udruženja Srbije
T2 - Arhiv za farmaciju
T1 - Clinical pharmacokinetics of methotrexate in the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients
T1 - Klinička farmakokinetika metotreksata u terapiji akutne limfoblastne leukemije i ne-Hodkinovog limfoma u pedijatrijskoj populaciji pacijenata
VL - 70
IS - 1
SP - 20
EP - 23
DO - 10.5937/arhfarm2001020X
ER -
@article{
author = "Škorić, Biljana and Jovanović, Marija and Miljković, Branislava and Kuzmanović, Marko and Vučićević, Katarina",
year = "2020",
abstract = "High dose methotrexate (MTX) is used in therapy of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients. It acts as competitive inhibitor of dihydrofolate reductase and consequently inhibits synthesis of deoxyribonucleic acid. The bioavailability is dependent upon dose and route of administration. The drug is moderately bound to plasma proteins and distributes in body tissues and cells. After the administration in high doses, MTX partially undergoes hepatic and intracellular metabolism, but renal excretion of parent compound is the main route of elimination. Numerous factors may influence pharmacokinetics and concentration of drug, but primarily the effect of renal function on elimination is described. Delayed elimination might also be the consequence of drug interaction in renal tubules. Toxicity can arise with high MTX doses, especially in patients with delayed MTX elimination. Therapeutic drug monitoring is indicated due to safety reasons, in order to optimize leucovorin (folinic acid) administration as it reduces MTX toxicity. Considering the variability and the toxicity of high dose MTX therapy, special caution is required in pediatric patients., Metotreksat (MTX) se u visokim dozama koristi u terapiji akutne limfoblastne leukemije i ne-Hodkinovog limfoma u pedijatrijskoj populaciji. Deluje kao kompetitivni inhibitor dihidrofolat reduktaze i time inhibira sintezu dezoksiribonukleinske kiseline. Stepen biološke raspoloživosti zavisi od puta primene leka i doze. Vezivanje za proteine plazme je u umerenom stepenu, a raspodeljuje se u tkiva i ćelije. Nakon primene u visokim dozama MTX delimično podleže hepatičkom i intracelularnom metabolizmu, ali glavni put eliminacije je preko bubrega u nepromenjenom obliku. Veliki broj faktora utiče na farmakokinetiku i koncentraciju leka, a pre svega je opisan uticaj funkcije bubrega na eliminaciju. Usporena eliminacija može biti i posledica interakcije sa drugim lekovima na nivou transportera u renalnim tubulima. Primena visokih doza MTX nosi rizik od pojave toksičnosti, posebno pri usporenoj eliminaciji. Terapijsko praćenje leka je indikovano iz bezbednosnih razloga, kako bi se optimizovala primena leukovorina (folinska kiselina) koji smanjuje toksičnost MTX. Imajući u vidu varijabilnost i toksičnost pri primeni visokih doza MTX poseban oprez je potreban u pedijatrijskoj populaciji pacijenata.",
publisher = "Beograd : Savez farmaceutskih udruženja Srbije",
journal = "Arhiv za farmaciju",
title = "Clinical pharmacokinetics of methotrexate in the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients, Klinička farmakokinetika metotreksata u terapiji akutne limfoblastne leukemije i ne-Hodkinovog limfoma u pedijatrijskoj populaciji pacijenata",
volume = "70",
number = "1",
pages = "20-23",
doi = "10.5937/arhfarm2001020X"
}
Škorić, B., Jovanović, M., Miljković, B., Kuzmanović, M.,& Vučićević, K.. (2020). Clinical pharmacokinetics of methotrexate in the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients. in Arhiv za farmaciju
Beograd : Savez farmaceutskih udruženja Srbije., 70(1), 20-23.
https://doi.org/10.5937/arhfarm2001020X
Škorić B, Jovanović M, Miljković B, Kuzmanović M, Vučićević K. Clinical pharmacokinetics of methotrexate in the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients. in Arhiv za farmaciju. 2020;70(1):20-23.
doi:10.5937/arhfarm2001020X .
Škorić, Biljana, Jovanović, Marija, Miljković, Branislava, Kuzmanović, Marko, Vučićević, Katarina, "Clinical pharmacokinetics of methotrexate in the treatment of acute lymphoblastic leukemia and non-Hodgkin lymphoma in pediatric patients" in Arhiv za farmaciju, 70, no. 1 (2020):20-23,
https://doi.org/10.5937/arhfarm2001020X . .
