milmedВоенная медицинаMilitary Medicine2074-5044Белорусский государственный медицинский университетmilmed-482Research ArticleОРИГИНАЛЬНЫЕ НАУЧНЫЕ ПУБЛИКАЦИИ. Лечебно-профилактические вопросыORIGINAL SCIENTIFIC PUBLICATIONS. Medical and preventive questionsМетотрексат в ротовой жидкости и риск развития химиотерапевтического мукозитаMethotrexate in saliva and risk in the development of chemotherapeutic mucositis in childrenПопруженкоТ. В.PapruzhenkaT. V.БорисС. П.BorysS. P.КраськоО. В.KraskoO. V.УО «Белорусский государственный медицинский университет»Belarus201719102026044345Copyright © Попруженко Т.В., Борис С.П., Красько О.В., 20262026Попруженко Т.В., Борис С.П., Красько О.В.Papruzhenka T.V., Borys S.P., Krasko O.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://milmed.ejournal.by/jour/article/view/482

Для оценки возможной роли прямого воздействия метотрексата (МТХ) на слизистую оболочку полости рта (СОПР) в развитии орального мукозита (ОМ) при противоопухолевой химиотерапии (ХТ) изучены параметры концентрации МТХ в биожидкостях 21 ребенка в течение 27 эпизодов ХТ с МТХ в режимах 1, 2 или 5 г/м2 площади поверхности тела за 24 ч (в т. ч. 4 эпизодов с ОМ) – в образцах ротовой жидкости (РЖ), взятых на 6-й, 12-й, 24-й, 42-й, 48-й, 54-й ч, и крови, взятых на 42-й, 48-й, 54-й ч от начала инфузии МТХ.Установлено, экскреция МТХ в полость рта повторяет алгоритм клиренса МТХ в крови, при этом концентрация МТХ в РЖ составляет, как правило, менее 1/10 от таковой в крови, в течение первых суток находится на децимикромолярном, а затем до 54 ч – на сантимикромолярном уровнях. У детей, имевших впоследствии ОМ, концентрация МТХ в РЖ на 6-й,12-й и 24-й ч была вдвое ниже, чем у детей без ОМ (р < 0,001), в последующие часы значимых различий в параметрах этих подгрупп не было. Эти данные не поддерживают гипотезу об участии слюнного МТХ в патогенезе ОМ.

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.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.

онкологиягематологияхимиотерапиядетиоральный мукозитвысокодозный метотрексатслюнакровьoncologyhematologychemotherapychildrenoral mucositishigh dose methotrexatesalivabloodReferencesAlbertioni, F. Monitoring of methotrexate and 7-hydroxy­ methotrexate in saliva from children with acute lymphoblastic leukemia receiving high-dose consolidation treatment: relation to oral mucositis / F. Albertioni, C. Rask, H. Schroeder, C. Peterson // Anticancer Drugs. – 1997. – Vol. 8, N 2. – P. 119–124.Albertioni, F. Monitoring of methotrexate and 7-hydroxy­ methotrexate in saliva from children with acute lymphoblastic leukemia receiving high-dose consolidation treatment: relation to oral mucositis / F. Albertioni, C. Rask, H. Schroeder, C. Peterson // Anticancer Drugs. – 1997. – Vol. 8, N 2. – P. 119–124.Dhiman, M. K. А Transbuccal Delivery of 5-Fluorouracil: Per­meation Enhancement and Pharmacokinetic Study / M. K. Dhiman, A. Dhiman, K. K. Sawant // AAPS PharmSciTech, – 2009. – Vol. 10, N 1. – P. 23–27.Dhiman, M. K. А Transbuccal Delivery of 5-Fluorouracil: Per­meation Enhancement and Pharmacokinetic Study / M. K. Dhiman, A. Dhiman, K. K. Sawant // AAPS PharmSciTech, – 2009. – Vol. 10, N 1. – P. 23–27.Epstein, J. B. The role of salivary function in modulating chemotherapy-induced oropharyngeal mucositis: a review of the literature / J. B. Epstein, A. H. Tsang, D. Warkentin // Oral Surg., Oral Med., Oral Pathol., Oral Radiolog., Endodont. – 2002. – Vol. 94, N 1. – P. 39–44.Epstein, J. B. The role of salivary function in modulating chemotherapy-induced oropharyngeal mucositis: a review of the literature / J. B. Epstein, A. H. Tsang, D. Warkentin // Oral Surg., Oral Med., Oral Pathol., Oral Radiolog., Endodont. – 2002. – Vol. 94, N 1. – P. 39–44.Hilal-Dandan, R. Manual of Pharmacology and Therapeutics / R. Hilal-Dandan, R. Brunton. – 2nd Ed.; Goodman and Gilman‘s, 2015. – 188 p.Hilal-Dandan, R. Manual of Pharmacology and Therapeutics / R. Hilal-Dandan, R. Brunton. – 2nd Ed.; Goodman and Gilman‘s, 2015. – 188 p.Ishii, E. Oral mucositis and salivary methotrexate con­centration in intermediate-dose methotrexate therapy for children with acute lymphoblastic leukemia / E. Ishii, S. Yamada, S. Higuchi // Med. Pediatr. Oncol. – 1989. – Vol. 17, N 5. – P. 429–432.Ishii, E. Oral mucositis and salivary methotrexate con­centration in intermediate-dose methotrexate therapy for children with acute lymphoblastic leukemia / E. Ishii, S. Yamada, S. Higuchi // Med. Pediatr. Oncol. – 1989. – Vol. 17, N 5. – P. 429–432.Maiguma, T. Relationship between oral mucositis and high-dose methotrexate therapy in acute lymphoblastic leukemia / T. Maiguma, Y. Hayashi, S. Ueshima // J. Clin. Pharmacol. Ther. – 2008. – Vol. 46, N 11. – P. 584–590.Maiguma, T. Relationship between oral mucositis and high-dose methotrexate therapy in acute lymphoblastic leukemia / T. Maiguma, Y. Hayashi, S. Ueshima // J. Clin. Pharmacol. Ther. – 2008. – Vol. 46, N 11. – P. 584–590.Oliff, A. Methotrexate-induced oral mucositis and salivary methotrexate concentrations / A. Oliff, W. A. Bleyer, D. G. Poplack // Cancer Chemother. Pharmacol. – 1979. – Vol. 2, N 3. – P. 225–256.Oliff, A. Methotrexate-induced oral mucositis and salivary methotrexate concentrations / A. Oliff, W. A. Bleyer, D. G. Poplack // Cancer Chemother. Pharmacol. – 1979. – Vol. 2, N 3. – P. 225–256.Patterson, A. J. Methotrexate serum and saliva concentrations in patients / A. J. Patterson, W. A. Ritschel, D. Zellner // Int. J. Clin. Pharmacol. Ther. Toxicol. – 1981. – Vol. 19, N 9. – Р. 381–385.Patterson, A. J. Methotrexate serum and saliva concentrations in patients / A. J. Patterson, W. A. Ritschel, D. Zellner // Int. J. Clin. Pharmacol. Ther. Toxicol. – 1981. – Vol. 19, N 9. – Р. 381–385.Raghavendra Rao, N. G. Overview on Buccal Drug Delivery Systems / B. Shravani, M. S. Reddy // J. Pharm. Sci. & Res. – 2013. – Vol. 5, N 4. – P. 80–88.Raghavendra Rao, N. G. Overview on Buccal Drug Delivery Systems / B. Shravani, M. S. Reddy // J. Pharm. Sci. & Res. – 2013. – Vol. 5, N 4. – P. 80–88.Schrøder, H. Lack of correlation between methotrexate concentrations in serum, saliva and sweat after 24h methotrexate infusions / H. Schrøder, K. B. Jensen, M. Brandsborg // Br. J. Clin. Pharmacol. – 1987. – Vol. 24, N 4. –P. 537–541.Schrøder, H. Lack of correlation between methotrexate concentrations in serum, saliva and sweat after 24h methotrexate infusions / H. Schrøder, K. B. Jensen, M. Brandsborg // Br. J. Clin. Pharmacol. – 1987. – Vol. 24, N 4. –P. 537–541.

The authors declare that there are no conflicts of interest present.