Klinička farmakokinetika metotreksata u terapiji akutne limfoblastne leukemije i ne-Hodkinovog limfoma u pedijatrijskoj populaciji pacijenata

  • Biljana Škorić Univerzitet u Beogradu, Farmaceutski fakultet, Katedra za farmakokinetiku i kliničku farmaciju
  • Marija Jovanović Univerzitet u Beogradu, Farmaceutski fakultet, Katedra za farmakokinetiku i kliničku farmaciju
  • Branislava Miljković
  • Miloš Kuzmanović - Univerzitet u Beogradu, Medicinski fakultet - Institut za zdravstvenu zaštitu zdravlja majke i deteta Srbije „Dr Vukan Čupić“
  • Katarina Vučićević Univerzitet u Beogradu, Farmaceutski fakultet, Katedra za farmakokinetiku i kliničku farmaciju
DOI: https://doi.org/10.5937/arhfarm70-24905

Sažetak


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 deoksiribonukleinske 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.

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Objavljeno
2020/02/29
Broj časopisa
Vol. 70 Br. Notebook 1 (2020): Arhiv za farmaciju
Rubrika
Pregledni (Revijalni) rad
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