phkineticaФармакокинетика и ФармакодинамикаPharmacokinetics and Pharmacodynamics2587-78362686-8830ООО «Издательство ОКИ»phkinetica-222Research ArticleТЕРАПЕВТИЧЕСКИЙ ЛЕКАРСТВЕННЫЙ МОНИТОРИНГTHERAPEUTIC DRUG MONITORINGВзаимосвязь между концентрацией циклоспорина в крови и тяжестью острой реакции «трансплантант-против хозяина» у детей после трансплантации стволовых клеток от подходящих родственных или неродственных доноровМартинП.clinvest@mail.ruБлейзакН.clinvest@mail.ruСуллеГ.clinvest@mail.ruГаламбрунК.clinvest@mail.ruБертранИ.clinvest@mail.ruМайерП.clinvest@mail.ruДжеллиффР.clinvest@mail.ruОланьеГ.clinvest@mail.ruДепартамент фармации госпиталя Дебрусс, ЛионFranceДепартамент фармации госпиталя Дебрусс, Лион; Госпиталь ФраншевилляFranceОтделение детской иммуногематологии и пересадки костного мозга госпиталя Дебрусс, ЛионFranceГоспиталь ФраншевилляFranceЛаборатория прикладной фармакокинетики Университета Южной Калифорнии, Лос-АнжелесUnited States20051103200502Клиническая фармакокинетика4048Copyright © Мартин П., Блейзак Н., Сулле Г., Галамбрун К., Бертран И., Майер П., Джеллифф Р., Оланье Г., 20052005Мартин П., Блейзак Н., Сулле Г., Галамбрун К., Бертран И., Майер П., Джеллифф Р., Оланье Г.Мартин П., Блейзак Н., Сулле Г., Галамбрун К., Бертран И., Майер П., Джеллифф Р., Оланье Г.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacokinetica.ru/jour/article/view/222

Для того, чтобы определить оптимальные концентрации циклоспорина (CsA) перед следующим введением (trough blood concentrations, TBC), необходимые пациенту в ранний послетрансплантационный период, были проанализированы соотношения между значениями TBC и острой реакцией «трансплантат-против хозяина» (РТПХ) у детей после операции по трансплантации стволовых клеток (SCT). 94 пациентам стволовые клетки были пересажены от подходящих родственных доноров (сибсы) (MSD) (n=36), неподходящих родственных доноров (MMRD) (n=3) или от неродственных доноров (UD) (n=55). Профилактика РТПХ обычно включала CsA или его комбинацию с метотрексатом (MTX). Антитимоцитарный глобулин добавлялся к терапии в случае UD-SCT. Концентрация циклоспорина в крови измерялась иммуноферментным методом (EMIT assay), а мониторинг и корректировка режима дозирования осуществлялись на основе байесовского подхода. Значения TBC, относящиеся к первым неделям после трансплантации, были оценены ретроспективно для каждого пациента на основе байесовского фармакокинетического моделирования, а затем статистически соотнесены с РТПХ. В случае MSD-SCT средние значения TBC во время первых двух недель после трансплантации были 42±10 нг/мл у пациентов со II-IV степенью РТПХ против 90±7 нг/мл у пациентов с 0-I степенью РТПХ (p=0,001). В случае UD или MMRD значения TBC были 73±4 нг/мл против 95±8 нг/мл, хотя этот тренд не был статистически значимым (p=0,284). Среди пациентов со значениями TBC > 85 нг/мл не было случаев РТПХ II-IV степени, в 10 случаях была незначительная РТПХ, а в 30 ее не было вообще. Среди пациентов со значениями TBC < 65 нг/мл у 7/11 пациентов после MSD-SCT и у 4/18 после UD — или MMRD-SCT развилась РТПХ II-IV степени. Средние значения TBC, соответствующие каждой степени РТПХ, были: без РТПХ 101±10 нг/мл, незначительная 77±11 нг/мл, средняя 61±13 нг/мл и тяжелая 56±15 нг/мл (p<0,001). Эти результаты выявили выраженное соотношение между значениями TBC в ранний посттрансплантационный период и тяжестью РТПХ у детей, перенесших MSD- и UD-трансплантацию стволовых клеток.

Опубликовано в журнале: Bone Marrow Transplantation 32:777-784, 2003. Relationship between CsA trough blood concentration and severity of acute graft-versus-host disease after paediatric stem cell transplantation from matched-sibling or unrelated donor

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