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Итулси- Itulsi/Ибранс — Ibrans (Палбоциклиб) 75 мг, 100 мг, 125 мг

Итулси (Палбоциклиб) 125 мг, Pfizer (Пфайзер), Германия (Европа)

Итулси- Itulsi/Ибранс — Ibrans (Палбоциклиб) 75 мг, 100 мг, 125 мг

Итулси — Ибранс (Палбоциклиб) — это препарат, который занимает важное место в лечении сложных форм рака молочной железы (РМЖ). Препарат значительно уменьшает активность клеток, за счет своей антимитотической способности, а также способствует старению и угнетению пролиферации опухоли.
Механизм действия препарата Итулси для борьбы с опухолевыми процессами связан с процессом ингибирования ферментных систем протеинкиназ. Активное вещество препарата Палбоциклиб.

Тестирование палбоциклиба на линий клеток РМЖ с установленными молекулярными профилями показало высокую эффективность препарата против ER-положительного (положительного по рецептору эстрогена) рака молочной железы. Клетки под действием палбоциклиб не переходят в фазу репликации ДНК, из-за чего становится невозможным их деление. Дополнительный прием антиэстрогенных средств играет положительную роль в терапии за счет уничтожения стимулов роста. Опухолевые единицы замедляют свой метаболизм и гораздо быстрее вступают в период старения (апоптоза).

Категория:

Описание

Итулси — Ибранс (Палбоциклиб) — это препарат, который занимает важное место в лечении сложных форм рака молочной железы (РМЖ). Препарат значительно уменьшает активность клеток, за счет своей антимитотической способности, а также способствует старению и угнетению пролиферации опухоли.
Механизм действия препарата Итулси для борьбы с опухолевыми процессами связан с процессом ингибирования ферментных систем протеинкиназ. Активное вещество препарата Палбоциклиб.

Главная роль активного вещества состоит в приостановке цепочки активации пролиферации злокачественных клеток. Палбоциклиб ингибирует циклинзависимые протеинкиназы CDK4 и CDK6. Палбоциклиб представляет собой высоко селективный, обратимый низкомолекулярный ингибитор циклин-зависимых киназ (CDK) 4 и 6. Циклин D1 и киназы CDK4/6 входят в состав сигнальных механизмов, активизирующих пролиферацию клеток. Ингибируя их палбоциклиб подавляет пролиферацию клеток за счет ингибирования перехода клетки из G1-фазы в S-фазу клеточного цикла.

Тестирование палбоциклиба на линий клеток РМЖ с установленными молекулярными профилями показало высокую эффективность препарата против ER-положительного (положительного по рецептору эстрогена) рака молочной железы. Клетки под действием палбоциклиб не переходят в фазу репликации ДНК, из-за чего становится невозможным их деление. Дополнительный прием антиэстрогенных средств играет положительную роль в терапии за счет уничтожения стимулов роста. Опухолевые единицы замедляют свой метаболизм и гораздо быстрее вступают в период старения (апоптоза).

Состав Итулси — Ибранс (Палбоциклиб)

1 капсула содержит:

  • активное вещество: палбоциклиб 75 мг, 100 мг, 125 мг.
  • дополнительные вещества: целлюлоза микрокристаллическая, карбоксиметилкрахмал натрия, лактозы моногидрат, диоксид кремния коллоидный, стеарат магния.
  • состав желатиновой капсулы: корпус капсулы – желатин, краситель железа оксид красный, краситель железа оксид желтый, титана диоксид; крышечка капсулы — желатин, краситель железа оксид красный, краситель железа оксид желтый, титана диоксид.
  • cостав чернил: шеллак, титана диоксид, изопропанол, аммиака раствор, пропиленгликоль, бутанол С, симетикон.

Показания к применению Итулси — Ибранс (Палбоциклиб)

  • в комплексе с гормонотерапией для лечения метастатического или местнораспространенного РМЖ, ER-положительного по гормональным рецепторам и отрицательного по рецептору эпидермального фактора роста человека 2-го типа (HER2),
  • в комплексе терапии в сочетании с ингибитором ароматазы в качестве 1 -й линии терапии,
  • в комплексе терапии в сочетании с фулвестрантом у женщин, получавших предшествующую терапию,
  • в комплексе терапии с агонистом лютеинизирующего гормона -рилизинг гормона (ЛГРГ) у женщин в пре- или перименопаузе.

Фармакодинамика

Анализ механизма действия показал, что взаимодействие палбоциклиба и антиэстрогенных средств усиливает реактивацию белка ретинобластомы (Rb) путем ингибирования фосфорилирования Rb, что ведет к подавлению передачи сигналов E2F и замедлению пролиферации. Усиление задержки пролиферации линий ER-положительных клеток рака молочной железы, обработанных антиэстрогенными средствами и палбоциклибом, одновременно происходит с усилением старения клеток, что влечет к длительному ингибированию клеточного цикла и увеличению размера клеток, относящемуся к фенотипу старения. По данным in vitro исследований на ксенотрансплантационных моделях из полученных из клеток ER-положительного рака молочной железы было показано, что взаимодействие летрозола и палбоциклиба дополнительно усиливает подавлениие процесса фосфорилирования Rb, а следовательно и дальнейшее распространение сигналов и дозозависимый рост опухоли. Это показывает участие задержки пролиферации, связанной со старением клетки, в качестве одного из способа, создающих противоопухолевую эффективность комбинированного действия палбоциклиба и антагониста ER на моделях ER-положительного РМЖ.

Фармакокинетика

Фармакокинетика палбоциклиба была описана на здоровых добровольцах и на пациентах с солидными опухолями, включая распространенный рак молочной железы.

Всасывание

Значение максимальной концентрации (Сmах) палбоциклиба в целом достигается через 6-12 часов (Сmах) после перорального приема. После перорального приема дозы 125 мг средняя абсолютная биодоступность палбоциклиба составляет 46 %. значения площади под кривой «концентрация время» (AUC) и максимальной концентрации в целом возрастают пропорционально дозе в диапазоне доз от 25 мг до 225 мг. Равновесное состояние достигается в течение 8 дней после повторных приемов препарата один раз в сутки. При повторных приемах один раз в сутки идет кумуляция палбоциклиба, при этом средний коэффициент накопления равен 2,4 (в диапазоне: 1,5-4,2).

Влияние приема пищи

При приеме натощак приблизительно в 13 % популяции всасывание и экспозиция палбоциклиба были очень низкими. Прием еды увеличивал экспозицию палбоциклиба в небольшой группе популяции, но не менял экспозицию палбоциклиба до клинически значимой величины у остальной части популяции.
В сравнении с приемом натощак, значения AUC и Сmах палбоциклиба повышались на 21 % и 38 % при приеме с пищей с высоким содержанием жира, на 12 % и 27 % при приеме с едой с низким содержанием жира и на 13 % и 24 %, если питание с умеренным содержанием жира принимали за один час до и через два часа после приема препарата. Также, прием еды существенно снижал вариабельность значений определения экспозиции палбоциклиба как между разными участниками, так и у одного и того же участника. Исходя из результатов, препарат необходимо принимать вместе с едой.

Распределение

Взаимодействие палбоциклиба с белками плазмы крови in vitro составляло примерно 85 %, при этом в диапазоне концентраций 500-5000 нг/мл зависимости от концентрации не наблюдалось. Среднее значение свободной фракции палбоциклиба в плазме крови человека in vivo увеличивалось при нарушении функции печени, при нарушении функции почек отсутствовали.

Метаболизм

Исследования in vitro и in vivo свидетельствуют, что в печени человека палбоциклиб подвергается интенсивному метаболическому пробразованию. После приема внутрь разовой дозы 125 мг палбоциклиба основные способы первичного метаболизма палбоциклиба состояли из окисления и сульфирования, а ацилирование и глюкуронирование служили минорными механизмами. Палбоциклиб был основным циркулирующим в плазме крови соединением. Основным циркулирующим метаболитом был конъюгат палбоциклиба с глюкуроновой кислотой. Большинство материала было выведено как метаболиты. Основным компонентом в кале был конъюгат палбоциклиба с сульфаминовой кислотой, который составлял 25,8 % от введенной дозы. Исследования in vitro показали, что в метаболизме палбоциклиба в главным образом участвуют изофермент SULT2A1 и CYP3A.

Элиминация

У лиц с распространенным раком молочной железы клиренс палбоциклиба составлял 63,08 л/час, а средний период полувыведения составлял 28,8 часа. У 6 здоровых добровольцев мужского пола, получивших разовую пероральную дозу палбоциклиба, среднее количество от 91,6 % от суммарной введенной радиоактивно меченой дозы было выведено через 15 дней; основным способом элиминации было выведение через кишечник (74,1 % от дозы), и 17,5 % дозы выводилось через почки. Выведенный в неизменном виде палбоциклиб, составлял в кале и моче 2,3 % и 6,9 % введенной дозы соответственно.

Применение у детей

Не исследовалась фармакокинетика палбоциклиба у пациентов в возрасте 18 лет и младше.

Применение у пожилых пациентов

Различий в эффективности или безопасности у больных в возрасте 65 лет и старше по сравнению с более молодыми пациентами не было отмечено.

Нарушение функции печени

По результатам исследования фармакокинетики у больных с различной степенью нарушения функции печени в сравнении с пациентам с больными с нормальной функцией печени показано, что свободная AUС уменьшалась на 17% у пациентов с нарушением функции печени легкой степени и повышалась на 34 % и на 77 % у пациентов с нарушением функции печени умеренной и тяжелой степени соответственно. Пиковая экспозиция свободного палбоциклиба увеличивалась на 7 %, 38 % и 72 % при нарушении функции печени легкой, умеренной и тяжелой степени соответственно, в сравнении с больными с нормальной функцией печени.К тому же, на основании результатов фармакокинетического популяционного анализа данных 183 пациентов с распространенным онкологическим заболеванием, среди которых у 40 больных было легкое нарушение функции печени, нарушение функции печени легкой степени не оказывало влияния на фармакокинетику.

Нарушение функции почек

По результатам исследования фармакокинетики у больных с различной степенью нарушения функции почек показано, что общая экспозиция палбоциклиба увеличивалась на 39 %, 42 % и 31% при нарушении функции почек легкой, умеренной и тяжелой степени соответственно,в сравнении с больными с нормальной функцией почек. Пиковая экспозиция палбоциклиба увеличивалась на 17 %, 12 %, и 15 % при нарушении функции почек легкой, умеренной и тяжелой степени соответственно, в сравнении с больными с нормальной функцией почек. К тому же, на основании результатов фармакокинетического популяционного анализа данных 183 пациентов с распространенным онкологическим заболеванием, среди которых у 73 пациентов было легкое нарушение функции почек и у 29 пациентов было умеренное нарушение функции почек, показано, что такие нарушения функции почек не оказывают влияния на фармакокинетику препарата. Фармакокинетику палбоциклиба у пациентов, которым требовался гемодиализ, не исследовали.

Фармацевтические характеристики

Капсулы твердые желатиновые.Капсулы светло-оранжевого цвета, с крышечкой и надписью «Рfizer». Бывают в трех дозировках:

  • 75 мг (размером № 2, с надписью белого цвета: «РВС 75»),
  • 100 мг (размером № 1, с надписью белого цвета «РВС 100»),
  • 125 мг (размером № 0, с надписью белого цвета: «РВС 125»).

Содержимое капсул — порошок от почти белого до желтого цвета.

Упаковка, срок годности, условия хранения

Капсулы 75 мг, 100 мг и 125 мг:

  • в ПЭВП флаконе по 21 капсуле с полипропиленовой крышкой. Горлышко флакона запечатано защитным диском из фольги. Каждый флакон с инструкцией упакован в пачку картонную.
  • в блистере из ПВХ/ПХТФЭ/ПВХ по семь капсул. По три блистера вместе с инструкцией по применению упакованы в пачку картонную.

Рекомендуется хранить при температуре до 30 °С и в недоступном для детей месте.

Срок годности 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.

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    Nevertheless, the proliferation of counterfeit products and unregulated suppliers makes it crucial for consumers to approach this market with
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    With a stable status as the #1 supplier of Canadian steroids, GHCanada ensures
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    Most users of Anavar discover they’ll increase muscle size, muscle voume, and overall strength.

    It can take a quantity of months on your testosterone to recover its normal perform after finishing an Anavar cycle.
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    Earlier Than you purchase Anavar or some other kind of steroids on-line, you must make certain that the seller
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    In the start, you’re in all probability not ready to make use of
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    Anavar is an unlawful drug in the UK and it is not worth
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    Anavar is a synthetic anabolic steroid that has been used by bodybuilders and
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