British journal of clinical pharmacology · 2023
Effects of ABCB1 polymorphisms on the transport of ponatinib into the cerebrospinal fluid in Japanese Philadelphia chromosome-positive acute lymphoblastic leukaemia patients.
СтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод пока не подготовлен
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Fukushi Yayoi, Akamine Yumiko, Abumiya Maiko, Tozawa Nagi, Yamashita Takaya, Nara Miho, Kameoka Yoshihiro, Takahashi Naoto, Miura Masatomo
Аннотация
The effects of polymorphisms of ABCB1 and ABCG2 on the dose-adjusted plasma trough concentrations and cerebrospinal fluid (CSF)-to-plasma ratios of ponatinib were evaluated. Blood (C4 ) and CSF (CSF4 ) concentrations at 4 h after administration were determined. The median (95% confidence interval) CSF4 -to-C4 ratio of ponatinib in subjects homozygous for ABCB1 variants 1236T/T, 2677T/T + T/A or 3435T/T were significantly higher than that in a group of subjects with other genotypes (P = .026, .012 and .015, respectively). The median (95% confidence interval) CSF4 -to-C4 ratio of ponatinib in 4 patients with the combination of ABCB1 variants 1236T/T-2677T/T + T/A-3435T/T was 2.62% (1.42-3.42%); this ratio was significantly higher than that in subjects with other genotypes (1.08% [0.89-1.47%]; P = .006). The brain distribution of ponatinib was affected by ABCB1 polymorphisms and therefore seems to be modulated by P-glycoprotein at the blood-brain and blood-CSF barriers.