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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

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2020
Clinical_pharmacokinetics_of_pub_2020.pdf (520.8Kb)
Authors
Škorić, Biljana
Jovanović, Marija
Miljković, Branislava
Kuzmanović, Marko
Vučićević, Katarina
Article (Published version)
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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 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.

Keywords:
methotrexate / pediatric population / pharmacokinetics parameters / rug interactions, / toxicity / metotreksat / farmakokinetički parametri / pedijatrijska populacija / terakcije lekova / toksičnost
Source:
Arhiv za farmaciju, 2020, 70, 1, 20-23
Publisher:
  • Beograd : Savez farmaceutskih udruženja Srbije
Funding / projects:
  • Basic and Clinical Pharmacological research of mechanisms of action and drug interactions in nervous and cardiovascular system (RS-175023)

DOI: 10.5937/arhfarm2001020X

ISSN: 0004-1963

Scopus: 2-s2.0-85081595278
[ Google Scholar ]
URI
https://farfar.pharmacy.bg.ac.rs/handle/123456789/3596
Collections
  • Radovi istraživača / Researchers’ publications
Institution/Community
Pharmacy
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 . .

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