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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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    in relative terms, based mostly on the amount of muscle mass
    they have. A full body exercise plan solely has you train 3
    days a week, which suggests there are one other 4 days
    to relaxation and get well. Until you attempt to purposely mess up your coaching, you’re going
    to have adequate time to totally recuperate between periods.

    Simple carbohydrates similar to white bread and white potatoes are primarily fast digesting simple sugars.
    These kinds of carbs will sometimes spike your insulin and result in a crash.
    Whey protein powder is another great method to get a quick serving of high quality protein.
    A typical bodybuilding coaching program will utilize 3 sets or four sets of
    an train for anyplace from eight reps to 15 reps, with 10 reps or 12 reps being frequent as well.
    Anyplace from three days to six days per week may be dedicated to coaching, with
    four days or 5 days being quite frequent. Vince Gironda’s 8×8 workout
    routine is an advanced bodybuilding routines designed to
    shock your muscles into progress.
    However, you have still obtained yet one more set to compete — just like the final one.
    You’ve Got received 2 minutes to relaxation (I suggest mendacity on the floor!) earlier than you get underneath the rack once more.
    To reap the advantages of eccentric coaching, and to increase your time
    beneath pressure, simply lower the burden at a slower pace than you raise it.
    By concentrating on the unfavorable, you’ll be able to take 4 seconds to decrease it.
    This is exceedingly tough since you are combating the pressure of gravity, however it’s also very efficient.

    But first, we need to reply the following query in the the way to build muscle puzzle.

    Like to me, you shouldn’t be specializing in quantity for hypertrophy.
    The first a quantity of months should simply be centered on studying your movement patterns and very basic kind routines.

    I would say that the number of exercises per muscle per week you want
    to have in your plan is one thing like 2 to 4. As A Result Of I’m bringing you unique insights from 7
    of the world’s smartest hypertrophy scientists.

    Utilizing their research, I’ll create a step-by-step blueprint that can function your final
    muscle-building hack.
    Traditional push-ups are usually carried out with the hands simply outdoors
    of shoulder width to permit the pecs to do a lot of the work.
    But bringing your arms in and tucking your elbows can produce higher muscle
    activity in both the triceps and the pecs. You can go one arm or two,
    seated or standing, and in case you have a associate, you’ll be able to go heavy and do some
    forced reps. Beta Alanine may also assist you to
    enhance the intensity of your workouts. As talked about, I is not going to go into too
    much depth however present sufficient for you to understand the basics to vitamin and supplementation when constructing muscle.

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