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.
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.
Keywords
About the Authors
T. V. PapruzhenkaBelarus
S. P. Borys
Belarus
O. V. Krasko
Belarus
References
1. 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.
2. 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.
3. 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.
4. Hilal-Dandan, R. Manual of Pharmacology and Therapeutics / R. Hilal-Dandan, R. Brunton. – 2nd Ed.; Goodman and Gilman‘s, 2015. – 188 p.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
Review
For citations:
Papruzhenka T.V., Borys S.P., Krasko O.V. Methotrexate in saliva and risk in the development of chemotherapeutic mucositis in children. Military Medicine. 2017;(4):43-45. (In Russ.)
JATS XML