42 KB292 KB37 KB200220262010Kmetec, VojkoSonc, MonikaTavčar, Petra10 straništevilka:4letnik:49str. 160-169ISSN:0351-0026COBISSID:2899825URN:URN:NBN:SI:doc-NFD0LIHXslInštitut za varovanje zdravja Republike SlovenijeZdravstveno varstvoBloodDrug interactionsDrug therapyfarmakokinetikainterakcijeLymphomaMethotrexatemetotreksatNeoplasmsonkologijaOsteosarcomaPharmaokineticsserumske koncentracijeTherapeutic usetherapyzdravljenjeProblematika visokih odmerkov metotreksata pri onkoloških bolnikih| Problems of high-dose methotrexate in oncological patients|Background: High-dose methotrexate is the only agent used in cancer therapy that requires routine measurements of serum concentrations to avoid potentially fatal high doses of methotrexate. The drug is used to treat osteosarcomas and non-Hodgkinćs lymphomas. As serum levels of methotrexate in patients treated at the Institute of Oncology were often elevated, we undertook this study to identify the parameters that increase serum methotrexate levels. Patients and Methods: All patients receiving a one-year course of high-dose methotrexate (n=20) were included in the study, regardlessof whether they had elevated or normal serum concentrations of methotrexate. Altogether, they received 55 high-dose methotrexate therapies. The following parameters likely to affect serum concentrations of methotrexatewere investigated: drug manufacturer, the person preparing the infusion, body mass index, patientćs age, creatinine clearance, estimated creatinine clearance, urine pH, concomitant chemotherapy with procarbazine, concomitant therapy with omeprazole, aspirin and nonsteroidal antirheumatic drugs. Interactions were statistically evaluated using the c2-test. Results: In 28 of the 55 therapies there was at least one case of elevated methotrexateconcentrations. Serum methotrexate concentrations in patients withlymphomas were significantly increased in elderly patients, in patients with high body mass index, those with creatinine clearance of < 100ml/min, andin patients on procarbazine or omeprazole therapy. Conclusions: In order toavoid adverse side-effects of high-dose chemotherapy, the dosage of methotrexate should be carefully adjusted in accord to important factors that may increase its concentration, and possible interactions with other drugs should be preventedIzhodišča: Metotreksat v visokih odmerkih je edini citostatik v onkologiji, kimu rutinsko določamo serumske koncentracije, saj je v visokih odmerkih potencialno smrten. Uporablja se za zdravljenje osteosarkomov in ne- Hodgkinovih limfomov. Ker so bile serumske koncentracije metotreksata pri bolnikih na Onkološkem inštitutu pogosto povišane, nas je zanimalo, kateri parametri jih zvišujejo. Bolniki in metode: V analizo smo vključili vse bolnike, ki so v enem letu prejeli metotreksat v visokih odmerkih, ne glede nato, ali so bile serumske koncentracije metotreksata povišane ali normalne. Gre za 20 bolnikov, ki so skupaj prejeli 55 visokodoznih terapij metotreksata.Pregledali smo, ali na serumske koncentracije metotreksata vplivajo parametri, kot so proizvajalec metotreksata, pripravljalec infuzije, indeks telesne mase, starost pacienta, očistek kreatinina, ocenjeni očistek kreatinina, pH urina, sočasna kemoterapija s prokarbazinom, sočasna terapija zomeprazolom, acetilsalicilno kislino in nesteroidnimi antirevmatiki. Medsebojne vplive smo statistično ovrednotili s c2-testom. Rezultati: Med 55 visokoodmernimi terapijami smo pri 28 terapijah ugotovili vsaj eno povišano koncentracijo metotreksata. Ugotovili smo, da so bile koncentracije metotreksata v serumu bolnikov z limfomi značilno povišane pri starejših bolnikih, pri bolnikih z vi{jim indeksom telesne mase, z očistkom kreatinina pod 100ml/min, in v primeru, da so bolniki sočasno z metotreksatom jemali prokarbazin ali omeprazol. Zaključki: Da bi se izognili neželenim učinkom visokoodmerne kemoterapije, bi bilo treba skrbno prilagoditi visoki odmerek metotreksata glede na pomembnejše dejavnike, ki lahko zvišajo njegovo koncentracijo, in preprečiti interakcije z drugimi zdraviliTEXTznanstveno časopisjejournalsSlovenian National E-content AggregatorNational and University Library of SloveniaInštitut za varovanje zdravja RS