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Нинларо — Ninlaro (иксазомиб)

Нинларо — Ninlaro (иксазомиб)

Препарат Нинларо (иксазомиб) − первый и единственный пероральный ингибитор протеасом для лечения пациентов с рецидивирующей и/или резистентной множественной миеломы, использующийся в комбинации с леналидомидом и дексаметазоном. Нинларо – выпускается в виде капсул для приема внутрь один раз в неделю.
Действующее вещество Нинларо — Иксазомиб является селективным и обратимым ингибитором протеасомы, обладающим высокой противоопухолевой активностью и прекрасным профилем безопасности.

Описание

Препарат Нинларо (иксазомиб) − первый и единственный пероральный ингибитор протеасом для лечения пациентов с рецидивирующей и/или резистентной множественной миеломы, использующийся в комбинации с леналидомидом и дексаметазоном. Нинларо – выпускается в виде капсул для приема внутрь один раз в неделю.
Действующее вещество Нинларо — Иксазомиб является селективным и обратимым ингибитором протеасомы, обладающим высокой противоопухолевой активностью и прекрасным профилем безопасности.

Состав

  • активное вещество: иксазомиба цитрат: 3,29/4,3/5,7 мг, что соответствует иксазомибу — 2,3/3/4 мг;
  • вспомогательные вещества: МКЦ; тальк; магния стеарат;
  • оболочка капсулы, дозировка 2,3 мг: желатин; титана диоксид; краситель железа оксид красный; чернила черные 10А21;
  • оболочка капсулы, дозировка 3 мг: желатин; титана диоксид; краситель железа оксид черный; чернила черные 10А21;
  • оболочка капсулы, дозировка 4 мг: желатин; титана диоксид; краситель железа оксид красный; краситель железа оксид желтый; чернила черные 10А21;
  • чернила черные 10А2 содержат: шеллак, калия гидроксид, пропиленгликоль, краситель железа оксид черный.

Фармакодинамика

Иксазомиб является обратимым ингибитором протеасом. Иксазомиб в основном взаимодействует и подавляет химотрипсиноподобную деятельность субъединицы бета-5 20S протеасомы.
Нинларо индуцирует апоптоз у культивируемых клеточных линий множественной миеломы in vitro. In vitro нинларо демонстрировал цитотоксичность в отношении клеток миеломы, взятых у больных с развившимися рецидивами после многократных циклов терапии, включавших бортезомиб, дексаметазон и леналидомид. Комбинация нинларо и леналидомида демонстрировала синергическое цитотоксическое действие на клеточные линии множественной миеломы. В условиях in vivo нинларо демонстрировал противоопухолевое воздействие на модели опухолевого ксенотрансплантата множественной миеломы мышей.

Кардиоэлектрофизиология

Иксазомиб не удлинял интервал QTc при воздействиях, соответствующих клиническим, по результатам фармакокинетическо-фармакодинамического анализа данных 245 пациентов.

Фармакокинетика

Всасывание

После приема внутрь медиана времени достижения максимальной концентрации нинларо в плазме была равна одному часу. Значение абсолютной биодоступности после перорального приема составляло 58% по результатам популяционного анализа фармакокинетики.
Кривая AUC нинларо повышается дозозависимым способом в диапазоне доз от 0,2 до 10,6 мг. По данным исследований влияния приема пищи, проведенное у больных, получавших однократную дозу 4 мг нинларо, показало, что пища с высоким содержанием жиров понижала AUC иксазомиба на 28% и максимальную концентрацию на 69%.

Распределение

Связывание нинларо с белками плазмы составляет 99%, распределяется в эритроциты, происходит с соотношением «кровь-плазма». Объем распределения в равновесном состоянии составляет 543 литров.

Метаболизм

После перорального приема дозы с радиоизотопной меткой иксазомиб представлял 70% всего связанного с препаратом радиоактивного материала в плазме. Основным механизмом выведения препарата нинларо считают метаболизм под действием множественных ферментов CYP и не-CYP белков. Эксперименты in vitro с применением изоферментов цитохрома Р450, произведенных на основе человеческой комплементарной ДНК, показали, что при клинически значимых уровнях концентрации иксазомиба не существует специфического изофермента CYP, главным образом участвующего в метаболизме иксазомиба. При более высоких концентрациях, чем клинические, иксазомиб подвергался метаболизму под действием многих изоформ CYP.

Выведение

По результатам фармакокинетического популяционного анализа клиренс составлял около 1,9 л/час с изменчивостью индивидуальных значений величиной 44%. Период полувыведения иксазомиба в конечной фазе составлял 9,5 суток. При пероральном еженедельном использовании отношение кумуляции было определено как двукратное.

При пероральном приеме однократной дозы меченого 14С-иксазомиба у 5 больных с распространенной злокачественной опухолью 62% поступившей радиоактивности было выведено с мочой и 22% с калом. Неизменный препарат, выведенный с мочой, составлял <3.5% введенной дозы.

Особые группы пациентов

Возраст, пол, этническая принадлежность. Не наблюдалось клинически значимого влияния возраста (в диапазоне 23-91 года), расовой принадлежности, пола или площади поверхности тела (диапазон 1,2-2,7 кв.м.) на клиренс нинларо на основании фармакокинетического популяционного анализа.

Нарушения функции печени.

Фармакокинетика иксазомиба у пациентов с нормальной функцией печени была сходной с таковой у пациентов с нарушениями функции печени легкой степени (общий билирубин ≤ВГН и АСТ>ВГН, или общий билирубин >1-1.5×ВГН и любое значение АСТ) на основании популяционного анализа фармакокинетики.

Фармакокинетические данные были описаны у пациентов с нормальной функцией печени при приеме иксазомиба в дозе 4 мг (n=12), с умеренными нарушениями функции печени при дозе 2.3 мг (общий билирубин >1.5-3×ВГН, n=13) или тяжелыми нарушениями функции печени при дозе 1.5 мг (общий билирубин > 3 × ВГН, n=18). Нормализованные по дозе средние значения AUC были на 20% выше у пациентов с умеренными или тяжелыми нарушениями функции печени по сравнению с пациентами с нормальной функцией печени.

Нарушения функции почек.

Фармакокинетика иксазомиба у пациентов с нормальной функцией почек была сходной с таковой у пациентов с нарушениями функции почек легкой или умеренной степени тяжести (КК ≥ 30 мл/мин) на основании фармакокинетического популяционного анализа.

Фармакокинетические данные были описаны при дозе иксазомиба 3 мг у пациентов с нормальной функцией почек (КК ≥ 90 мл/мин, n=18), тяжелыми нарушениями функции почек (КК < 30 мл/мин, n=14) или с заболеваниями почек в терминальной стадии, требующими диализа (n=6). Средние значения AUC были на 39% выше у пациентов с тяжелыми нарушениями функции почек или с заболеваниями почек в терминальной стадии, требующими диализа, по сравнению с пациентами с нормальной функцией почек. Нинларо не выводится при проведении диализа, о чем свидетельствует, то что концентрации препарата перед диализом, во время его проведения и после проведения диализа были сходными.

Показания препарата

  • в комбинации с дексаметазоном и леналидомидом применяется для лечения больных с множественной миеломой, получивших ранее как минимум одну линию терапии.

Описание лекарственной формы

  • Капсулы, 2,3 мг: твердые, желатиновые, № 4. Корпус и крышечка капсулы — светло-розового цвета, имеется надпись, нанесенная черными чернилами «Takeda» — на крышечке «2.3 mg» — на корпусе.
  • Капсулы, 3 мг: твердые, желатиновые, № 4. Корпус и крышечка капсулы — светло-серого цвета, имеется надпись, нанесенная черными чернилами «Takeda» — на крышечке и «3 mg» — на корпусе.
  • Капсулы, 4 мг: твердые, желатиновые, № 3. Корпус и крышечка капсулы — светло-оранжевого цвета, имеется надпись, нанесенная черными чернилами «Takeda» — на крышечке и «4 mg» — на корпусе.

Фармацевтические характеристики

Содержимое капсул — порошок от белого до желтовато-белого цвета.

Упаковка, срок годности, условия хранения

По 1 капсуле в ПВХ Алюминий/Алюминий блистер. Блистер герметично вклеен в картонную обложку и неотделим от нее. По одной картонной обложке вместе с инструкцией по применению помещают в пачку картонную. Три картонные пачки помещают в общую картонную пачку. На защитной наклейке голографическим способом указывают логотип «Takeda».

Срок годности — 3 года.

Хранить при температуре не выше 30°С. Не замораживать. Хранить в оригинальной упаковке непосредственно до приема каждой капсулы. Хранить в недоступном для детей месте.

 

 

 

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 Нинларо (иксазомиб) в Алматы

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Позвоните и узнайте цену Нинларо (иксазомиб)

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

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    Here we’ve a full body dumbbell exercise that is great for building durability and brute power.

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    It includes a knee drive and a bicep curl as you carry out the step up,
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    The activation loop area is outlined by the start of the DFG motif
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    If you’re the writer of this article, you don’t want to request permission to breed figures and diagrams offered correct
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    Get a great stretch every rep and totally contract at the prime (even barely exaggerating the vary of motion by moving the dumbbell up higher
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    We’re going to record the highest 15 and following the record will talk about each individually.

    The finest workout on your objectives is one that fits your unique needs—your age, fitness level,
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    By incorporating superior strategies, understanding the precept of
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    Embrace the challenge, enjoy the journey, and witness the transformative
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    cardiovascular conditioning. For males seeking to break obstacles of their fitness journey, these routines offer a versatile, challenging, and environment friendly methodology.

    An overview of the cryo-EM picture processing work-flow of the MD-(ATPγS) data is proven in Supplementary Fig.
    The DH was phosphorylated by 400 nM DDK for 30 min at 24 °C in pre-RC
    buffer. After washing with pre-RC buffer, the DH-DDK complicated was eluted by AluI (NEB,
    R0137L) in buffer C (25 mM HEPES/KOH pH 7.5, 5 mM MgAc,
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    The eluate was crosslinked with 0.1% glutaraldehyde (agar scientific,
    R1020) for 15 min on ice. ORC, Cdc6, Cdt1, and MCM2-7 had been purified as previously described23.

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    Whereas you can’t fully isolate any space, decrease chest workouts will hone in on the lower a part of the sternocostal
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    It can strengthen your muscle tissue and improve your bone density, while
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    Whether Or Not you address these elements in their own contexts or
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    This part collects any data citations, data availability
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    Furthermore, the Dbf4 SCR forms a lasso round probably the
    most N-terminal resolved region of Mcm4 and in this means could contribute in the
    direction of the specificity of Cdc7 to Mcm4 (Fig. 4b-III).
    A large number of backbone-to-backbone contacts, within the
    lasso construction latching on Mcm4, could accommodate similar binding modes when binding and phosphorylating different DDK substrates.

    The dumbbell jumping lunge is an explosive exercise that is going to work your legs, core, arms and traps.
    Nonetheless, this is primarily a dumbbell leg train, and due to the explosiveness of the movement, one of the primary advantages of this exercise is elevated calorie burn. As such, the principle goal of the dumbbell squat press
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    So, if you are in search of an athletic based mostly whole physique dumbbell exercise that fills a lot of wants with one deed, it is a nice one.

    A dumbbell advanced is a series of dumbbell exercises performed consecutively without rest.

    One set of every train is completed earlier than shifting
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    The goal is to have interaction multiple muscle teams,
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    Together these Dbf4-Mcm interactions place Cdc7 on the MCM2-7 double-hexamer in a novel method (Fig. 1d), which shields the
    kinase area from N-terminal extensions of different Mcm proteins other than the Mcm4-N-terminal
    tail. Thus, the observed kinase-substrate interaction is enhancing
    substrate choice for Mcm4. Substrate interplay III (SIII) involves a Dbf4 motif -M and -C connector (aa509–538),
    which is very conserved between different species of budding yeast (Fig. 4b-III, Supplementary Fig. 5b).
    Apparently, a piece of area III (aa509–538; labelled as SCR in Fig. 1e–g) is situated in shut proximity
    to the Cdc7 P-loop and generates a floor along the energetic site cleft of Cdc7
    instantly opposite the substrate-binding web site. Kinases mainly type transient, weak interactions with their substrates involving a small region alongside
    the cleft of the kinase active site47. Weak interactions allow for fast launch
    of the substrate once phosphorylation has occurred. This secure
    interplay presents the chance to characterise the big DDK-substrate
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    If you are doing a body half split, you will have a workout
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    It is necessary to note that because the weights do not
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