Methotrexate in saliva and risk in the development of chemotherapeutic mucositis in children

Abstract

The aim of the study was to assess the possible direct effect of anticancer therapy with methotrexate (MTX) in bio liquids on the oral mucosa in the development of oral mucositis (OM). Twenty one children and adolescents participated in this study. Chemotherapy with MTX was administered in the following concentrations of 1; 2; 5 g/m2 of body surface area during 24 hours (including four episodes with OM). Twenty seven episodes of chemotherapy with high dose MTX were assessed in the samples of saliva on the 6th; 12; 24; 42; 48; 54 hour from the start of infusion and in the samples of blood on the 42; 48; 54 hour from the start of infusion. Сoncentration of methotrexate was measured by standard fluorescent polarization immunoassay using MTX reagent pac kit according to the manufacturer's instructions. Analysis of dynamics of methotrexate concentration in samples was performed using a linear model of mixed effects, on the basis of which the average values ​​(M) and confidence intervals for them were calculated (95 % CI). The analysis of the correlation of the levels of methotrexate in the blood and oral liquid was performed at individual time points (42; 48 and 54 hours) using the Spearman method (r). It was determined that excretion of MTX in the oral cavity repeated its clearance in blood. MTX concentration in saliva was less than 1/10 from its concentration in blood. During the first day, MTX concentration had decimicromol level and then until 54 hour it had santimicromol level. MTX concentration in saliva on the 6; 12; 24 hour in children with OM was lower by 2 times than in children without OM (P < 0,001). There was no significant difference in those parameters between two groups (with or without OM) in the following observed hours. This data does not support hypothesis concerning involvement of salivary MTX in OM pathogenesis.