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Бартизар — Bortezomib (Бортезомиб) 3,5 мг №1 флакон

Бартизар — Bortezomib (Бортезомиб) 3,5 мг №1 флакон

Компания Medical&Pharma предлагает современное лекарство Бартизар (Бортезомиб). Оно относится к группе противоопухолевых препаратов, у которого в качестве активного вещества содержится бортезомиб (в форме трехмерного бороксина). Препарат назначается пациентам с мантийноклеточной лимфомой, а также миеломными новообразованиями. Противоопухолевая эффективность объясняется фармакологическими свойствами его структурных компонентов. На данный момент, бортезомиб — это одно из известнейших противоопухолевых средств в мире. Лекарство было синтезировано в 1995-м году, согласно клиническим данным было показано, что за счет подавления скорости нейтрализации протеасомных клеток, бортезомиб замедляет рост миеломных новообразований. На сегодняшний день в терапии онкологических больных с миеломами бортезомиб признан основным лекарственным препаратом.

Описание

Компания Medical&Pharma предлагает современное лекарство Бартизар (Бортезомиб). Оно относится к группе противоопухолевых препаратов, у которого в качестве активного вещества содержится бортезомиб (в форме трехмерного бороксина). Препарат назначается пациентам с мантийноклеточной лимфомой, а также миеломными новообразованиями. Противоопухолевая эффективность объясняется фармакологическими свойствами его структурных компонентов. На данный момент, бортезомиб — это одно из известнейших противоопухолевых средств в мире. Лекарство было синтезировано в 1995-м году, согласно клиническим данным было показано, что за счет подавления скорости нейтрализации протеасомных клеток, бортезомиб замедляет рост миеломных новообразований. На сегодняшний день в терапии онкологических больных с миеломами бортезомиб признан основным лекарственным препаратом.

Бортезомиб оказывает непосредственное влияние на процесс нейтрализации патологических новообразований, путем обеспечивания активности белковых комплексов, борющихся со злокачественными клетками.

Состав

Бартизар — Bortezomib

  • бортезомиб (в форме трехмерного бороксина) 3.336 мг
  • в одном флаконе содержание бортезомиба в форме мономера составляет 3.5 мг
  • вспомогательные вещества: маннитол — 35 мг

Показания

  • Множественная миеломные образования.
  • Пациенты с мантийноклеточной лимфомой, ранее получивших, по крайней мере, первую линию терапии.

Фармакокинетика

После однократного струйного в/в ведения двухфазно снижается концентрация бортезомиба в плазме крови. После первого введения Бортезомиб быстрее выводится по сравнению с последующими. Период полувыведения вещества колеблется от 5 до 15 ч на начальной фазе распределения.

Биодоступность бортезомиба в диапазоне доз 1-1.3 мг/м2 увеличивается пропорционально дозе, в диапазоне доз от 1.45 до 2 мг/м2 имеет дозозависимый характер.

После многократного введения наблюдается снижение клиренса бортезомиба, что приводит к соответствующему увеличению периода полувыведения (T1/2). На кинетику начального распределения вещества повторные введения не влияют, и Сmax и T1/2 величины не изменяются в этой фазе. После введения третьей дозы в первом цикле лечения величина AUC увеличивается — с 30.1 до 54 ч/нг/мл, а средний срок выведения лекарства в конечной фазе увеличивается с 5.45 до 19.7 ч. Связывание бортезомиба с белками плазмы крови при концентрациях 0.01-1 мкг/мл составляет 82.9%. Доля лекарства, связавшегося с белками плазмы крови, от концентрации не зависит.

В условиях in vitro метаболизм бортезомиба преимущественно осуществляется при участии изоферментов цитохрома Р450 — CYP3A4, CYP2C19 и CYP1А2. Неизмененный бортезомиб лишь в небольшом количестве выводится с мочой, не обнаруживается в желчи и кале.

У пациентов с множественной миеломой, после однократного или многократного введения лекарства в дозах 1 и 1,3 мг/м2 средний Vd бортезомиба составляет 1659–3294 л (489–1884 л/м2). Это позволяет предположить, что в периферических тканях бортезомиб интенсивно распределяется. Связывание препарата с белками плазмы крови, при концентрациях бортезомиба 100–1000 нг/мл, составляет в среднем 83%.

Основной механизм метаболизма вещества осуществляется путем отщепления атомов бора с образованием двух метаболитов, которые в дальнейшем образуют несколько других метаболитов путем гидрокслирования. Протеасому 26S метаболиты бортезомиба не ингибируют.

У человека пути выведения бортезомиба не изучались.

На фармакокинетику бортезомиба влияние возраста, расы и пола не изучались.

У больных со средними и тяжелыми степенями нарушения функции печени, по сравнению с пациентами с нормальной функцией печени, наблюдается 60% увеличение AUC лекарства. Рекомендуется уменьшение начальной дозы бортезомиба и внимательное наблюдение пациентов с нарушениями функции печени средней и тяжелой степени. На фармакокинетику вещества  легкие нарушения функции печени не влияют.

В дозах 0,7–1,3 мг/м2 в/в 2 раза в неделю фармакокинетикой бортезомиба, у пациентов с легкими, средними, тяжелым нарушениями функции почек, а также пациентов, находящихся на диализе, сравнима с фармакокинетикой лекарства у пациентов с нормальной функцией почек.

Фармакодинамика

Бортезомиб представляет собой модифицированную борную кислоту, это высокоселективный обратимый ингибитор активности протеасомы 26S. Протеасома 26S является ключевым компонентом клеток и присутствует в ядре и цитозоле всех эукариотических клеток, катализируя расщепление основных белков, участвующих в управлении жизненным циклом клеток. Химотрипсиноподобное действие протеасомы ингибирует бортезомиб, вызывает торможение протеолиза, что приводит к апоптозу.

К апоптозу, вызванному бортезомибом, миеломные клетки почти в 1000 раз более восприимчивы, чем нормальные клетки плазмы.

Способность бортезомиба блокировать активацию NF-kB является основным фактором, объясняющим способность ингибитора протеасомы бортезомиба уничтожать клетки миеломы. В нормальных здоровых клетках NF-kB (существует ввиде димера р50-р65) находится в неактивной форме в цитозоли, так как связан с ингибирующим белком LkB. В процессе активирования формы NF-kB важную роль играет протеасома, она катализирует разрушение ингибирующего белка LkB, тем самым активирует протеолитическую генерацию NF-kB р50. Такой активированный NF-kB проникает в ядро, помогает опухолевой клетке выжить и пролиферировать. Блокируя протеасому и, таким образом, тормозя активацию NF-kB, бортезомиб способствует уменьшению количества антиапоптозных факторов, воспалительных молекул, цитокинов (которые стимулируют рост клеток миеломы) и молекул клеточной адгезии (которые позволяют соединительным клеткам прикрепляться к клеткам костного мозга).

На многих экспериментальных моделях, включая множественную миелому бортезомиб вызывает замедление роста человеческих опухолей.

Фармацевтические

характеристики

Производится и отпускается в виде в виде лиофилизированной массы или порошка белого или почти белого цвета для приготовления раствора для в/в и п/к введения.

Упаковка, срок годности,

условия хранения

Лекарство помещают во флакон из бесцветного стекла, с резиновыми пробками и алюминиевыми колпачками,который содержит свой серийный номер и упакован в картонную упаковку.  В каждую картонную упаковку с лекарственным средством помещается также инструкция по использованию препарата.

Хранить в упаковке, защищая от солнечного света и влаги, в недоступном для детей месте, при температуре не выше 25 градусов по шкале Цельсия. Готовый раствор необходимо использовать в течение 8 часов.

Срок годности составляет 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 Бартизар (Бортезомиб) в Алматы

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Позвоните и узнайте цену Бартизар (Бортезомиб)

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

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    Carry Out every transfer for 40 seconds, then relaxation for
    20 seconds to complete 1 spherical. Perform the total
    sequence for 3 rounds for one of the best muscle-building
    effect, with a minute between rounds. YOU DON’T NEED a ton of equipment to get a
    well-rounded exercise. Whereas your fitness center could
    also be stacked wall-to-wall with every piece of drugs conceivable,
    don’t let the flowery machines and instruments distract from the helpful fundamentals,
    just like the almighty dumbbell.
    You’ll need different equipment, like benches, for a few of
    them, whereas others can be completed with only one or two
    weights and your willpower to sweat. Complexes is normally a phenomenal conditioning device,
    in addition to a power booster. Sure, you are utilizing weight
    far less than you’ll on single-set workouts, however the longer
    time underneath rigidity your muscular tissues are subjected to nonetheless supplies
    a great stimulus for growth. You also can get an enormous metabolic effect, allowing your physique to continue
    burning calories long after you leave the gym. That’s
    simply not the case with conventional cardio periods.
    Whereas complexes are extremely efficient thanks to the fact that they prevent from having to jump around the gym to make the most of different gear and/or space, they’re also brutally
    effective. In Contrast To traditional single set workout routines, complexes can be
    incredibly taxing and sometimes result in complete system fatigue.

    Carry Out 7 reps of every train, then take a fast rest and
    repeat for 2 to three whole rounds. It can strengthen your muscular tissues and enhance your bone density, whereas additionally bettering your
    mobility. On A Daily Basis tasks like carrying heavy grocery bags will
    feel much easier. When folks begin exercising at home, they often veer
    towards actions that promise to burn calories
    shortly. For instance, working or high-intensity interval training (HIIT)
    workouts for fat loss. «By holding a dumbbell in front of your chest, the biceps, shoulders and upper back also become involved in the movement.»
    Ultimately, this permits you to take stress off
    your joints and place them on the muscle tissue (where they belong).

    Here is an example of how a great chest and back dumbbell exercise may look.
    Begin each workout with a 5-10 minute dynamic heat up to
    ensure your muscle tissue and joints are primed. As with all flys, keep your arms locked
    into place with a slight bend and squeeze your pecs to
    move the dumbbell up somewhat than just your arms and lower
    down slowly to essentially feel the stretch. Your chest is made up of two muscle tissue on each side — the pectoralis main and pectoralis minor,
     referred to as the pecs. You can hit the gym and pull from a rack full of
    dumbbells, or prepare at residence with an adjustable pair that gives
    you entry to only as many choices. I lately started a
    dumbbell routine and just accomplished my first week.

    The handheld weights are easier to wrangle than the lengthy, inflexible,
    heavy barbells that populate bench press stations and squat racks in gyms, however they’re also sturdy
    sufficient to lifted, swung, carried, and more.
    I maintain my rest intervals reasonable ( seconds), and infrequently go
    over 5 rounds (mainly as a outcome of doing so would kill me or leave
    me puking away all my precious nutrients). These complexes can be 
    finest served on the finish of a energy training day,
    and even as a standalone exercise. Complicated training is a time-saving,
    space-saving method of training that can be smartly programmed as a half of a exercise,
    or as its own workout. They make the most of the same piece of kit
    for a collection of workouts accomplished in succession,
    with out placing the weight down between. They’re nice for conditioning,
    cardiorespiratory endurance, and simply for efficient metabolic
    training for fats loss. Depending on the load and rep ranges used, they can be effective for building muscle (the similar
    method compound sets can be).
    This EMOM workout of the day includes performing
    four jumping exercises – squat bounce, leaping lunges,
    box jump, and knee tap. Since all are plyo workout routines, it will be challenging, so attempt to handle it based on your fitness
    degree. The final exercise in the dumbbell complicated is the dumbbell flat bench
    press. The subsequent exercise of the dumbbell complicated is the dumbbell
    push press.
    When the dumbbells are overhead and almost touching, squeeze your chest and return them to the starting
    place via that same path of movement, then repeat.
    The dumbbell around the world isn’t a extensively known exercise, however it doesn’t imply it’s not effective.
    This exercise is nice for the chest and shoulders, but you must have healthy shoulders to
    carry out it as it strikes your shoulder blades through a extensive variety of motion.
    The one arm chest press is the same because the flat bench press but you’ll only be using one dumbbell and focusing on one facet at a time.

    This is as a outcome of they include a predetermined sequence
    of lifts—i.e., you pick up weight and don’t set it down till
    you’re carried out with the advanced. For occasion, in complex 1, the clear will be your limiting factor.
    Choose the burden that’s acceptable for cleans all through the rounds, and use that same set of dumbbells for the Romanian deadlift and row.

    Now determine the load of the dumbbells you used in probably the most difficult train in Step 2 (when you were
    determining your 5RM). The most challenging exercise will be the one by
    which you used the lightest weight. As Soon As
    you might have that number, plug it into the following method to determine your load
    (weight of dumbbells) for the advanced. Even circuit
    coaching — typically hailed because the cardio king of
    the burden room — appears lazy compared. Lastly, lunges are
    a great train for building the glutes, unilateral strength, and balance.
    Most of us have a stronger aspect, and unilateral workout routines corresponding to
    this one let you give attention to every leg independently.
    To carry out thrusters, simply do a full entrance squat and use the momentum on the concentric rep to «drive» the burden up
    overhead in one movement.
    The dumbbell leaping lunge is an explosive exercise that
    is going to work your legs, core, arms and traps. Nevertheless, that is primarily a
    dumbbell leg exercise, and thanks to the explosiveness of the motion, one of
    the main benefits of this exercise is increased calorie burn. As such, the main target of the dumbbell squat press
    is the quads, glutes, hamstrings, shoulders, chest, and even your
    biceps. Moreover, it additionally requires your core and again to work isometrically as to take care of stability and an upright posture.
    So, in case you are in search of an athletic primarily based whole physique
    dumbbell train that fills plenty of wants with one deed, this is
    a nice one.
    Utilizing what you’ve received in a wise coaching technique ought to ameliorate the state of affairs.
    This allows you to work extra muscles, that means you’ll burn extra energy than you’ll with single-joint exercises.
    At first, complexes can appear to be the weightlifting equal of
    steady-state cardio.
    The second you get drained or sloppy throughout your coaching is the moment
    you’ve stopped building that reserve and began simply «working out».
    As within the case of fat burning ambitions, complete physique complexes are most likely to
    have the greatest impact on conditioning, and I can’t think of a single piece of apparatus that won’t
    get the job done. Because I was actually doing deadlifts, squats and barbell press variations almost daily – albeit
    with relatively gentle weight – I needed to be mindful of recovery.
    That said, I used a CNS faucet take a look at app on days I planned to finish with a HIIT session to make sure I was up for the task.

    On a side notice, I did not expertise much in the greatest way of muscle fatigue in any respect throughout the program.
    A Schematic illustration of the totally different levels of DDK recruitment
    to the MCM2-7 DH and different modes of binding. C Cartoon drawing of (b), with lacking structural regions extended as dotted
    lines.
    Together these Dbf4-Mcm interactions position Cdc7 on the MCM2-7 double-hexamer in a
    singular 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 noticed kinase-substrate interaction is enhancing substrate choice for Mcm4.
    Substrate interplay III (SIII) entails a Dbf4 motif -M and -C connector
    (aa509–538), which is very conserved between totally different species of budding yeast (Fig. 4b-III, Supplementary Fig. 5b).
    Curiously, a section of area III (aa509–538; labelled as SCR in Fig. 1e–g) is
    positioned in close proximity to the Cdc7 P-loop and generates a floor alongside the active
    website cleft of Cdc7 immediately opposite the substrate-binding site.
    Kinases primarily type transient, weak interactions with
    their substrates involving a small region alongside the cleft of the kinase active site47.

    Weak interactions allow for quick launch of the substrate
    once phosphorylation has occurred. This stable interaction provides the opportunity to characterise the large DDK-substrate interplay floor and examine
    how various structurally disordered Mcm N-termini are targeted for phosphorylation.
    ⊕ Carry Out three or 4 rounds of Complicated 1, resting 60 seconds between rounds.⊗ Relaxation as needed
    before moving on to the following advanced.
    When doing plank rows, I prefer to elevate my nonworking arm
    on a dumbbell so I get a full range of movement. Keep on monitor of your fitness with these
    quick but laser-focused exercises. I don’t need to begin sounding like an afterschool special, so I will hold this
    brief. The slightly longer answer is, it is decided by what
    type of hypertrophy you’re targeting. There are two usually
    accepted forms of hypertrophy that I briefly talked about
    in my Mikey and Mouth story earlier.
    Sure, they suck literally and figuratively, however they are efficient.
    Simply choose a muscle group that you need to destroy,
    and stack two to 4 exercises on high of it. In the presence of DDK,
    MCM2-7 itself appears comparatively static, fitting with the observation that the MCM2-7 DH phosphorylated by DDK has
    no giant conformational changes when compared to the unphosphorylated DH54.
    We didn’t observe the inhibitory area of Mcm4 (aa74–174), which becomes
    relieved upon DDK dependent MCM2-7 phosphorylation, so we cannot conclude on its structure24.

    Nonetheless, our data show that the Mcm6 zinc finger can nonetheless restrain initial DNA unwinding (Fig. 7e).

    As such, this exercise goes to work the legs, glutes,
    entrance delts, and serratus anterior, as properly as the higher chest to a level.
    The main goal of this train is the quads, glutes, biceps, and forearms, however your
    core and back will also be working exhausting to take care of stability and good posture.

    Ideally, each massive compound exercise in your workout could have
    at least two major muscle groups as the primary movers. Complexes are typically used
    as a conditioning methodology to skyrocket the center rate and burn fat.

    I like lifting up to now, however I’ve read in varied locations
    that you simply should not lift every day so as to allow for
    restoration. The rectus abdominis are answerable for the six-pack form on the front of the abdomen. These
    muscles are additionally pivotal for flexing (or bending) your
    backbone and offering core stability.
    If you discover T-push-ups too difficult, you can always modify them by preserving your knees on the
    floor (use padding if your knees are sensitive). Because kettlebells are irregularly formed,
    you’ll want to vary your grip transferring from one train to the following.
    Do this as quickly as potential, and don’t use these transitions
    as a chance for a sneaky relaxation.
    Regardless of how little the health club carries equipment-wise, we can typically count on the reality that dumbbells
    of various weights might be obtainable. For that reason, it makes sense to zero in on dumbbell complexes
    for varying objectives. This sequence works pushing patterns within the higher and decrease physique.

    The front squat builds leg strength with an upright posture
    that trains stability in the core. The curl and overhead press are basic moves
    to strengthen your arms and shoulders. Isaly (pictured here) designed this full-body advanced utilizing dumbbells.
    You can carry out each of the next complexes by
    itself as a mini-workout — try one when you’re quick on time or as a «finisher» on the finish of a exercise for added
    conditioning — or string them together.
    It entails a knee drive and a bicep curl as you
    perform the step up, which goes to work the hip flexors,
    biceps, and forearms, but in addition is going to noticeably take a look at your steadiness.
    To keep steadiness, your core and glutes/hip
    abductors are going to have to be absolutely engaged.
    So, if you have bother with common bodyweight solely planks, you may not be prepared for this.
    You are going to need some severe core strength and stability
    to carry out this exercise. Jumping with heavy kettlebells can put an extreme
    quantity of pressure on your backbone.
    E Simplified version of (c) showing a step-wise hypothetical mechanism
    of Mcm4 substrate localisation and processive phosphorylation. The area labelled 1,
    options part of Dbf4 SCR which varieties a hook (lasso) across the inflexible floor of Mcm4.
    The area labelled 2, options an encircled Mcm4 versatile tail
    that gets threaded via the kinase. The missing structural areas are represented as dotted lines and resolved regions as solid lines.
    Kinases frequently type fleeting interactions with their substrates.
    DDK is uncommon, as it types a steady complicated with MCM2-7 DH, which supports environment friendly phosphorylation of N-terminal tails of Mcm2,
    Mcm4 and Mcm612,thirteen. The DDK–MCM2-7 interactions stabilise flexible regions
    in Dbf4 and Cdc7, which significantly supported the
    structural analysis of the overall kinase complex and allowed
    us to explain the dynamic substrate engagement in immense element.

    B The Dbf4 SCR-G mutant was analysed for its interplay of DDK
    with MCM2-7 DH. Related results were obtained in three impartial experiments.
    C Volcano plot evaluating WT and SCR-G DDK phosphorylation of the MCM2-7 DH.
    Two-sample Student’s t-test carried out with three replicate intensities thought-about
    per group. P-values have been corrected for multiple comparisons to an FDR
    of 0.05 (permutation-based FDR). D Volcano plot important phosphosites visualised using HCA coupled to a heatmap of z-scored website intensities.

    These workouts alternate between intense bursts of activity and brief recovery intervals, maximizing calorie burn and muscle growth in a brief period
    of time. After I competed in Olympic lifting, I often used a modified Javorek barbell
    complex. It was mainly to arrange my body for heavy lifting and acted as a warm-up.
    However it additionally had a constructive effect on muscle mass and even conditioning.

    All that mystical crap that everyone appears to
    assume is optionally available like stretching and foam rolling is crucial.
    The older and extra energetic I get, the more I understand
    how necessary it is to cater to restoration. In fact, I’d argue that the effectiveness of your workout hinges more on the choices you make earlier than and after you truly
    put the work in.

    References:

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