Pediatric Hematology/Oncology and ImmunopathologyPediatric Hematology/Oncology and ImmunopathologyВопросы гематологии/онкологии и иммунопатологии в педиатрии1726-17082414-9314Fund Doctors, Innovations, Science for Children41610.24287/1726-1708-2020-19-4-20-31ПЕРЕДОВАЯ СТАТЬЯPharmacokinetics of 13-cis-Retinoic acid in high-risk neuroblastoma patientsФармакокинетика 13-цис-Ретиноевой кислоты у пациентов с нейробластомой группы высокого рискаhttps://orcid.org/0000-0002-6331-5339LitvinE. A.ЛитвинЕ. А.
Russian Federation

Evgeny A. Litvin, Cand. med. sci., Scientific at the Laboratory of Molecular Oncology

1 Samory Mashela St., Moscow 117997

Литвин Евгений Александрович, канд. мед. наук, научный сотрудник лаборатории молекулярной онкологии

117997, Москва, ул. Саморы Машела, 1

evgeny.litvin@fccho-moscow.ruhttps://orcid.org/0000-0001-7479-0007UtalievaD. T.УталиеваД. Т.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-3704-8783KachanovD. Yu.КачановД. Ю.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-2057-2036PshonkinA. V.ПшонкинА. В.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0003-3792-1682YadgarovM. Ya.ЯдгаровМ. Я.
Russian Federation

Moscow

Москва

https://orcid.org/0000-0002-3767-4477ShamanskayaT. V.ШаманскаяТ. В.
Russian Federation

Moscow

Москва

Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, Ministry of Healthcare of the Russian FederationФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России0812202019420312012202020122020Copyright ©; 2025, «D. Rogachev NMRCPHOI»Copyright ©; 2025, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России2025«D. Rogachev NMRCPHOI»ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава Россииhttps://creativecommons.org/licenses/by/4.0https://hemoncim.com/jour/article/view/416

13-cis-Retinoic acid is a differentiation agent for neuroblastoma cells and is a part of post-consolidation therapy for high-risk patients. The effectiveness of this therapeutic approach is currently under study. 26 patients with high-risk neuroblastoma treated at Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology were included in the study of 13-cis-Retinoic acid pharmacokinetics by high-performance liquid chromatography assay with ultraviolet detector depending on the method of administration of drug (swallowed capsules or opened capsules before administration). This study is supported by the Independent Ethics Committee and approved by the Academic Council of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The current study showed that the therapeutic concentration of > 2 μM when taking 13-cis-Retinoic acid at a dose of 160 mg/m2/day was achieved in two groups, regardless of the method of drug administration. However, plasma concentrations of 13-cis-Retinoic acid at 4 hours after administration on the 14th day of therapy were higher in the group of patients who swallowed the capsules (4.1 ± 1.8 μM), compared to those who could not do it (1.9 ± 1.5 μM) (p = 0.022). The introduction into the clinical practice of therapeutic drug monitoring of 13-cis-retinoic acid in high-risk neuroblastoma patients with an assessment of peak concentration and dose adjustment of the following courses may be an important point in the attempt to optimize postconsolidation therapy and improve prognosis.

13-цис-Ретиноевая кислота (13-цис-РК) является дифференцировочным агентом для клеток нейробластомы (НБ) и входит в состав постконсолидационной терапии пациентов группы высокого риска. Эффективность данного терапевтического подхода в настоящее время продолжает изучаться. В исследовании фармакокинетики методом высокоэффективной жидкостной хроматографии с ультрафиолетовым детектором в зависимости от способа приема 13-цис-РК (целые капсулы или извлечение препарата из капсул) включены 26 пациентов с НБ группы высокого риска, получавших лечение в ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России. Исследование показало, что терапевтической концентрации > 2 мкмоль/л при приеме 13-цис-РК в дозе 160 мг/м2 удалось достичь в обеих группах независимо от способа приема препарата. Однако содержание в плазме крови 13-цис-РК на 4 ч после введения на 14-й день терапии было выше в группе пациентов, принимавших целую капсулу (4,1 ± 1,8 мкмоль/л), чем в группе больных, которым для приема необходимо было вскрытие капсулы (1,9 ± 1,5 мкмоль/л) (р = 0,022). Внедрение в клиническую практику терапевтического мониторинга уровня 13-цис-РК в плазме крови у детей с НБ группы высокого риска с оценкой пиковой концентрации и коррекции дозы в последующих курсах может быть важным компонентом оптимизации постконсолидационной терапии, направленным на улучшение выживаемости.

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