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Рибомустин — Ribomustin (бендамустин)

Рибомустин — Ribomustin (бендамустин)

Рибомустин является химиотерапевтическим препаратом, используемым в качестве монотерапии или в комбинации с другими противораковыми средствами для лечения хронического лимфолейкоза, множественной миеломы и индолентной неходжкинской лимфомы. Действующее вещество препарата — Бендамустин.

Антинеопластическое свойство бендамустина было подтверждено в многочисленных экспериментах in vitro на различных опухолевых клеточных линиях (рак молочной железы, рак яичников, немелкоклеточный и мелкоклеточный рак легкого, различные виды лейкоза, а также рак толстой кишки, почечноклеточная карцинома, злокачественные новообразования предстательной железы, меланома и головного мозга) и in vivo – на различных исследуемых моделях опухолей (саркома, меланома, рак молочной железы, лимфома, лейкоз и мелкоклеточный рак легкого).

Описание

Рибомустин является химиотерапевтическим препаратом, используемым в качестве монотерапии или в комбинации с другими противораковыми средствами для лечения хронического лимфолейкоза, множественной миеломы и индолентной неходжкинской лимфомы. Действующее вещество препарата — Бендамустин.

Антинеопластическое свойство бендамустина было подтверждено в многочисленных экспериментах in vitro на различных опухолевых клеточных линиях (рак молочной железы, рак яичников, немелкоклеточный и мелкоклеточный рак легкого, различные виды лейкоза, а также рак толстой кишки, почечноклеточная карцинома, злокачественные новообразования предстательной железы, меланома и головного мозга) и in vivo – на различных исследуемых моделях опухолей (саркома, меланома, рак молочной железы, лимфома, лейкоз и мелкоклеточный рак легкого). Наличие перекрестной резистентности в человеческих опухолевых клеточных линиях с различными механизмами устойчивости была показано лишь в незначительной степени или ее отсутствие.

Показания к применению:

  • хронический лимфоцитарный лейкоз. Не была установлена эффективность применения в терапии первой линии по сравнению с другими химиопрепаратами кроме хлорамбуцила;
  • в монотерапии индолентной неходжкинской лимфомы у пациентов, у которых отмечалось прогрессирование на фоне или в течение 6 месяцев после окончания терапии с включением ритуксимаба;
  • множественная миелома II стадии с прогрессированием или III стадии (по классификации Дьюри-Сальмона) в сочетании с преднизолоном.

Состав

Порошок — 1 флакон содержит:

  • Активное вещество: бендамустина гидрохлорид 100 мг.
  • Вспомогательные вещества: маннитол — 120 мг.

Фармакодинамика

Противоопухолевое средство с бифункциональной алкилирующей активностью. Механизм действия главным образом связан с формированием перекрестных сшивок молекул одноцепочечной и двухцепочечной ДНК в результате алкилирования. Вследствии этого нарушается матричная функция ДНК и ее биосинтез. Имеются также данные о том, что бендамустин обладает дополнительными антиметаболическими свойствами (эффектом пуринового аналога).

Антинеопластическое свойство бендамустина было подтверждено в многочисленных экспериментах in vitro на различных опухолевых клеточных линиях (рак молочной железы, рак яичников, немелкоклеточный и мелкоклеточный рак легкого, различные виды лейкоза, а также рак толстой кишки, почечноклеточная карцинома, злокачественные новообразования предстательной железы, меланома и головного мозга) и in vivo – на различных исследуемых моделях опухолей (саркома, меланома, рак молочной железы, лимфома, лейкоз и мелкоклеточный рак легкого). Наличие перекрестной резистентности в человеческих опухолевых клеточных линиях с различными механизмами устойчивости была показано лишь в незначительной степени или ее отсутствие.

Это отчасти объясняется взаимодействием с ДНК, которое, по сравнению с другими алкилирующими средствами, дольше длится. Например, была обнаружена только частичная перекрестная резистентность с другими алкилирующими средствами, такими как циклофосфамид, кармустин или цисплатин.Также, в клинических исследованиях было обнаружено, что не существует полной перекрестной резистентности между бендамустином и алкилатами или антрациклинами.

Фармакокинетика

Распределение

После однократной 30-минутной в/в введении бендамустина в дозе 120 мг/м2 бета-фаза элиминации (T1/2β) составляет 28,3 мин. Объем распределения при 30-минутной в/в инфузии составляет 19,3 л, при дальнейшем систематическом введении и достижении равновесного состояния объема распределения — от 15,8 до 20,5 л. В системном кровотоке бендамустин активно связывается с белками плазмы (>95%), главным образом с альбумином.

Способность бендамустина к взаимодействию с белками плазмы крови не нарушается при низких концентрациях альбумина в плазме крови у больых в возрасте старше 70 лет и при поздних стадиях опухолей.

Метаболизм

Бендамустина гидрохлорид метаболизируется преимущественно в печени. Основным способом выведения бендамустина гидрохлорида из организма является его гидролиз с образованием моногидрокси- и дигидроксибендамустина. В образовании гамма-гидроксибендамустина (М3) и N-десметилбендамустина (М4) в печени задействован изофермент CYP1А2 цитохрома Р450. In vitro бендамустин не ингибирует CYP1А4, CYP2С9/10, СYP2D6, CYP2Е1 и CYP3А4.

Элиминация и экскреция

Среднее значение общего клиренса после 30-минутной в/в системы препарата 12 субъектам в дозе 120 мг/м2 составило 639,4 мл/мин. Около 20% введенной дозы препарата экскретировалось почками на протяжении 24 ч.

Количество экскретируемого с почками неизмененного бендамустина и его метаболитов располагается в порядке убывания следующим образом: моногидроксибендамустин > бендамустин > дигидроксибендамустин > окисленный метаболит > N-десметилбендамустин. С желчью выводятся преимущественно полярные метаболиты.

Фармакокинетика у различных групп пациентов

Пациенты с нарушенной функцией печени.

При 30–70% опухолевом поражении печени и незначительно сниженной функцией печени (сывороточный билирубин <1,2 мг/дл), фармакокинетика не имела значимых различий от таковой у больных с нормальной функцией печени и почек в отношении максимальной концентрации, Tmax, AUC, периоде полувыведения, объема распределения и выведения.

Пациенты с нарушением функции почек.

Фармакокинетические параметры у пациентов с клиренсом креатинина >10 мл/мин, в т.ч. находящихся на диализе, не отличались существенно от таковых у больных с нормальной функцией почек в отношении максимальной концентрации, Tmax, AUC, периоде полувыведения, объема распределения и выведения.

Пожилые пациенты.

Фармакокинетические параметры (пациентов старше 84 лет не включались в исследование фармакокинетики бендамустина) у лиц старше 18 и младше 84 лет значимо не различались.

Не обнаружено различий в фармакокинетике в зависимости от расы.

 

Фармацевтические характеристики

Порошок для приготовления концентрата для приготовления раствора для инфузий. Порошок белого цвета, лиофилизированный, микрокристаллический.

Упаковка, срок годности, условия хранения

  • дозирoвка 25 мг: во флаконах из коричневого стекла I типа объемом 26 мл с резиновой пробкой и съемным алюминиевым колпачком, предназначенным только для однократного использования, по 55 мг лиофилизированного порошка. Помещены в пачке картонной по 1, 5, 10 или 20 флаконов.
  • дозирoвка 100 мг: во флаконах из коричневого стекла I типа объемом 60 мл с резиновой пробкой и съемным алюминиевым колпачком, предназначенным только для однократного использования, по 220 мг лиофилизированного порошка. Помещен в пачке картонной по 1 или 5 флаконов.

Хранить препарат Рибомустин в защищенном от света месте, при температуре не выше 25 °C. Хранить в недоступном для детей месте.

Срок годности препарата Рибомустин 3 года.

 

 

 

 

Наша компания работает как на территории Казахстана, так и осуществляет доставку в страны ближнего зарубежья. Обращайтесь к нам за консультациями по контактным телефонам.

Заказать и купить Рибомустин (бендамустин) в Алматы

Заказать и купить Рибомустин (бендамустин) в Казахстане

Позвоните и узнайте цену Рибомустин (бендамустин)

Работаем и отправляем Рибомустин (бендамустин) по странам СНГ: Россия, Украина, Кыргызстан (Бишкек), Белоруссия, Узбекистан (Ташкент),
а также можем отправить Рибомустин (бендамустин) по регионам Казахстана: Нур-Султан (Астана), Шымкент, Талдыкорган, Актау и другие.

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