Описание
Препарат Милотарг (с действующим веществом — гемтузумаб озогамицин) 1 сентября был одобрен FDA для лечения взрослых с недавно диагностированным с CD33 позитивным острым миелоидным лейкозом. Препарат также получил одобрение для применения у детей старше 2-х лет с острым миелоидным лейкозом , клетки которого экспрессируют CD33. Белок CD33- это рецептор является маркером ОМЛ (острого миелоидного лейкоза), и характерен для 90% случаев острого миелолейкоза. Этот препарат был ранее одобрен для лечения взрослых пациентов с недавно диагностированным CD33-положительным ОМЛ. Также Гемтузумаб озогамицин одобрен в Европейском союзе для этой группы пациентов.
В 2000 году Милотарг уже был одобрен для применения. Впоследствии его сняли с применения, ввиду выявления риски для здоровья больных. В настоящий момент, препарат одобрен в другом терапевтическом режиме, для иной группы пациентов и в более низкой дозировке. В аннотации к препарату FDA разместила информацию о возможных побочных эффектах и рисках.
Лекарство помогает больному достичь полной ремиссии болезни и способствует гибели раковых клеток. Средство улучшает самочувствие пациента и устраняет выраженную симптоматику заболевания. На препарат Милотарг (гемтузумаб озогамицин) отзывы пациентов встречаются положительные. Отмечают меньшее проявление побочных реакций и высокую эффективность данного лекарственного средства.
Показания к применению
- для лечения впервые диагностированного CD33 позитивного острого миелоидного лейкоза у взрослых;
- для лечения рефрактерного и рецидивирующего острого миелоидного лейкоза с экспрессией CD33у взрослых и детей старше 2 лет.
Фармакодинамика
Милотарг — это таргетное лекартсво, которое представляет собой антитело, соединенное с токсичным противоопухолевым компонентом. К клеткам ОМЛ, экспрессирующим антиген CD33, он переносит гемтузумаб озогамицин. Раковые клетки перестают расти и гибнут.
Было показано в клинических исследованиях, что добавление препарата Милотарга к стандартной химиотерапии позволяет достигнуть более длительной ремиссии. Показатель выживаемости у пациентов, получавших гемтузумаб озогамицин, составил 4,9 месяца, а в группе паллиативной терапии – 3,6 месяца. Согласно результатам другого исследования, 26процентов пациентов, получавших гемтузумаб озогамицин, достигли полной ремиссии, средняя продолжительность которой составила 11,6 месяца.
Гемтузумаб озогамицин представляет собой рекомбинантное, гуманизированное моноклональное антитело против CD33, ковалентно взаимосвязанное с противоопухолевым цитотоксическим антибиотиком Калихеамицином (N-ацетил-калихеамином). Препарат был разработан для лечения острого миелоидного лейкоза (ОМЛ). В данном комплексе лекарственного средства и антитела, антитело избирательно взаимодействует и поглощается опухолевыми клетками, экспрессирующими антиген CD33. Присоединенный к антителу калихеамицин поставляется внутрь клеток опухоли экспрессирующей CD33 и прицельно уничтожает их. В результате достигается существенное снижение токсичности калихеамицина.
Действие Милотарга ведет к внутриклеточному освобождению диметилгидразина N-ацетил-гамма-калихеамицина путем гидролитического расщепления линкера. Активация диметилгидразида N-ацетил-гамма-калихеамицина вызывает разрывы двухцепочечной ДНК, что приводит к снижению роста раковых клеток. Препарат Милотарг активно взаимосвязывается с белками плазмы человека и метаболизируется путем неферментативного восстановления дисульфидной части.
Действие средства нацелено на купирование, а затем и уничтожение раковых клеток, согласно инструкции по применению Милотарга. В основе состава Милотарга лежит специальное антитело направленного действия. Милотарг направлен на ускорение ремиссии у пациентов, которые ранее его применяли в качестве основного средства при терапии острого миелоидного лейкоза (ОМЛ). Однако, с целью снизить риски для пациентов, схему терапии дополнили другими препаратами.
Компоненты гемтузумаб озогамицин распознают человеческий антиген CD33 и ингибируют активность опухоли. Под действием медикаментозного препарата происходит гидролитическое расщепление линкера. Лекарственное средство прерывает реакции, способствующих развитию болезни, и блокирует патологический клеточный цикл.
Этот препарат:
- разрывает способствующие развитию недуга реакции;
- останавливает болезнетворный цикл болезни;
- улучшает самочувствие, сглаживает и устраняет симптомы болезни;
- вызывает гибель раковых клеток;
- способствует достижению пациентом полной ремиссии при минимальных побочных явлениях.
Гемтузумаб озогамицин является CD33-направленным конъюгатом антитело-лекарственного препарат. Участок антитела (hP67.6) распознает антиген CD33 человека. N-ацетил гамма калихеамицин, представляет собой цитотоксический агент, которые ковалентно присоединен к антителу. Данные показывают, что противоопухолевая активность гемтузумаба озогамицина обусловлена связыванием с экспрессирующими CD33 опухолевыми клетками с конъюгатом антитело-лекарственное средство с последующей интернализацией комплекса А-ЛС-CD33 и внутриклеточного высвобождения диметилгидразида N-ацетил-гамма-калихеамицина путем гидролитического расщепления линкера. Активация диметилгидразида N-ацетил-гамма-калихеамицина вызывает разрывы двухцепочечной ДНК, что ведет к торможению клеточного цикла и апоптотической гибели клеток.
Фармакокинетика
При фракционированном режиме введения клинических данных фармакокинетического профиля гемтузумаба озогамицина нет. При вводении гемтузумаба озогамицина в дозе 9 мг/м² (2 дозы через 14 дней), максимальная концентрация после введения первой дозы составляла 3,0 мг/мл и увиличивалась до 3,6 мг/мл после второй инфузии.
Распределение
N-ацетил гамма калихеамицин диметилгидразид приблизительно на 97% связывается с белками плазмы человека in vitro. Общий объем распределения антитела hP67.6 составляет приблизительно 21,4 л.
Элиминация
Клиренс (CL) hP67.6 из плазмы составлял 0,35 л/часов после первой инфузии и 0,15 л/часа после второй инфузии препарата Милотарга. Период полувыведения из плазмы для hP67.6 составляет 62 часа после первой дозировки и 90 часов после второй дозировки.
Метаболизм
in vitro исследования показали, что диметилгидразид N-ацетил гамма калихеамицин главным образом интенсивно метаболизируется путем неферментативного восстановления дисульфидной части.
Меры предосторожности
- Гепатотоксичность, включая веноокклюзионную болезнь печени
Говорилось о случаях гепатотоксичности, включая опасные для жизни и иногда фатальные случаи веноокклюзионной болезни печени у пациентов.
- Инфузионные реакции, включая анафилаксию
В течение 24 часов во время или после инфузии могут возникать жизнеугрожающие или летальные инфузионные реакции . Симптомы и признаки и инфузионных реакций могут включать озноб, лихорадку, тахикардию, гипотонию, респираторную недостаточность и гипоксию.
- Кровотечения
Гемтузумаб озогамицин является миелосупрессором. Может вызвать опасные для жизни или смертельные кровотечения из-за развивающейся тромбоцитопении.
Упаковка, срок годности, условия хранения
Препарат выпускается в форме концентрата для внутривенных инъекций, во флаконах 4,5 мг.
Хранить следует в холодильнике, вдали от света. но не подвергать замораживанию, обеспечивая оптимальную температуру 2-8℃.
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 Милотарг (Гемтузумаб озогамицин) в Алматы
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Позвоните и узнайте цену Милотарг (Гемтузумаб озогамицин)
Работаем и отправляем Милотарг (Гемтузумаб озогамицин) по странам СНГ: Россия, Украина, Кыргызстан (Бишкек), Белоруссия, Узбекистан (Ташкент),
а также можем отправить Милотарг (Гемтузумаб озогамицин) по регионам Казахстана: Нур-Султан (Астана), Шымкент, Талдыкорган, Актау и другие.
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This program is superior, but you will only see optimal results in case your
nutrition and restoration are on point. With that
said, there’s nothing unique about what those ought
to seem like for this program, so this is just a good reminder.
Most athletes will select to do it from prime to bottom,
but you presumably can decide and choose which moves you need to do by which
order. I’ve colour coded the movements so that the primary actions are green or
gray.
Most consultants advocate starting together with your larger
muscle groups and continuing to the smaller ones. The
most demanding workouts are those carried out by your giant muscle groups, and you will
want your smaller muscular tissues to get the most out of these strikes.
Nonetheless, it may be exhausting to continue to challenge your physique
with none additional resistance, so to progress, you will want some tools.
Fortunately, there is loads of inexpensive residence fitness center gear available to get you began.
This data, however, doesn’t promise any advantages when misused or misinterpreted.
Powerlifting is a competitive sport that takes years of
exhausting work and consistent dedication to become proficient at.
This Powerlifting Program relies on the Mathias Methodology
Strength System. Since it has the high-frequency aspect working for it, it typically
proves to be successful. If you want to get good outcomes
with this program, eating a better calorie food plan shall be a
should to help the amount. Most people additionally
discover that they turn out to be hungrier while following this program, which is consultant of the extraordinary nature of it.
They quietly support your every move, maintain you upright, and assist you to raise
heavy stuff and perform day by day tasks with ease.
Ignore it, and also you might end up groaning every time you pick one thing up.
Not to mention that a muscular back makes you look good from all angles.
Do three exercises per week with no much less than in the future of relaxation in between, and
you’ll move the training days around to match your schedule.
Let’s say you needed to use a cut up training method
and trained your chest on at some point.
It’s instead been proven to grow probably the most from tricep workout routines
the place the arm is positioned overhead. To fix this, keep away from totally straightening your
legs at the start of every rep. Cease barely
short so your knees remain barely bent earlier than starting the subsequent rep.
This is in all probability going as a result of the seated place stretches
the hamstrings greater than the lying version — a stretch
that analysis suggests is a powerful driver of muscle growth.
One of those muscular tissues solely crosses the knee, so
its main position is to flex your knee, like in a leg curl.
Your biceps may try to take over the motion, particularly if your back is weaker or you’re using
an excessive quantity of weight. Most people’s higher chest is
underdeveloped in comparison with other areas, but it performs an enormous role in making a fuller, extra balanced
chest. Stick with one of many two plans supplied in this article for
8-12 weeks.
Research present that when youth are engaged in resistance coaching, their chances of sustaining an damage are
significantly reduced3. When you begin training in your teenagers, you begin studying these habits.
Many match people will tell you that going to the gym is just part of their day,
very related to brushing your tooth. Bear In Mind, knowing if a teenager has gone
by way of puberty plays a significant factor in figuring out
what the training program will look like.
As those niggles and aches begin to creep in it’s necessary that you simply keep your muscles, joints and connective tissues protected by preparing them properly before your exercises.
Preserving your muscle tissue robust and lean helps to enhance the method in which you
look, your bodily and practical skills and
also offsets pure muscle loss as a end result
of reduced testosterone and protein synthesis. However you’ll be
happy to know though that strength training has been proven to boost testosterone ranges
and go some way to reversing low T in males over 50 [6].
That is the weight that you will perform your
6 sets of 6 reps with. This is every week where you’ll
nonetheless get a great quantity of coaching volume in however
it will enable your physique to recover from the high-intensity work, and reduce your risk of injury.
Be sure to follow your lifts exactly how they’re supposed to be performed within the competitors.
This first section might final one month or one year, relying
on the place you began. Do two to three full-body workouts per week focusing on all the main muscle teams — chest, again, arms,
shoulders core and legs. When you are feeling stronger and
assured with these primary strikes, you can move
on to more difficult exercises using extra weight and depth.
They can give consideration to correct kind on the bench
press, dumbbell presses, numerous squats and
deadlifts and so forth.
Olympic weightlifting differs from other forms of weight training, like powerlifting, because it’s extra
about pace, method, and precision rather than just hoisting heavy weights.
Take lean physique weight in kilos and multiply by 1.0 to
calculate every day protein consumption in grams. This quantity should remain constant
on training and non-training days. So our man with 180 pounds of lean body
mass should consume 200g of protein daily. Multiply this
quantity by four to calculate what number of calories you’ll derive
from protein, so the 180-pound male would get
800 cal. As A Outcome Of you’ve educated your chest, again, and
shoulders heavy, you can actually give consideration to building and shaping your biceps and triceps with isolation actions.
(For example, for chest the dumbbell flye hits the pecs immediately, so your triceps shouldn’t end up being the weak link and cause the termination of the set during the bench press).
If you may have been following our 3 day newbie cut up workout
plan for mass and learnt workout routines correctly. This 4-day superior full-body exercise plan is made for individuals who have been lifting weights for no
much less than a 12 months. The routine lasts for three months and focuses on constructing muscle
mass.
A well-planned 3-day exercise routine incorporates necessary
principles of muscle building. Since you’re training six days
per week, following a well-structured workout program is
crucial because you can quickly overtrain. Two of the most well-liked 6-day workout splits include
the upper/lower and push/pull/legs split. A
6-day exercise break up may be very efficient for constructing
muscle, gaining energy, and losing fats, so lengthy as it’s
programmed properly. This overview of evaluations synthetizes the literature on the effect of train coaching programs on weight reduction,
physique composition modifications together with visceral adipose tissue, and weight upkeep.
Two essential research questions were not addressed in this overview.
When we discuss physical activity, we are referring to increasing your daily motion. Whereas
this will likely seem like exercise, the distinction comes from the purpose.
This allows probably the most quantity to be placed on each muscle group whereas nonetheless permitting an sufficient amount of exercise.
Luckily, a latest meta-analysis discovered that exercise effectively treats the signs and onset of migraines³.
Select a few exercises on your decrease body and a few in your higher body.
Simply doing squats and lunges is adequate to target
all the most important muscle groups of the decrease body — quads, hamstrings, calves and glutes.
You can target your shoulders, arms, back and chest with chest presses, pullups,
rows and navy presses. Your muscular tissues develop in between weight
training classes, not whilst you’re coaching. Therefore, you have to allow sufficient time earlier than training the
same muscle group once more. Prepare to maximise your strength with our exclusive 13-week power coaching program.
It is never too late to begin constructing lean muscle mass, levels of which start to decline after age
30, particularly amongst sedentary people.
Or you could have a busy week and can’t carry weights as
often as usual. If you repeat this cycle a couple of times,
like doing 3 sets of 10 bicep curls with relaxation in between, you’re in your
method to becoming a rep-and-set pro. Beginners might only do a set or two per exercise, while experienced
powerlifters can spend an hour or extra doing set after set
of the identical train. Science currently factors out that hitting sets per
muscle group per week is a good way to boost muscle mass and improve conditioning.
Going low carb can optimize insulin sensitivity,
that means you metabolize carbs more successfully so you may want to try it on a coaching or non-training day.
And bear in mind, don’t overcomplicate the process of gaining
mass! Simply stick to these basics and visualize yourself making positive
aspects. And if you focus on it, you’re additionally working the complete back-side of your
physique. This is a component that some may neglect because back and hamstrings aren’t as seen to us (or to the mirror!).
Another thing to suppose about is the breakdown of your
weight-training classes. Will you carry out total-body workouts or focus
solely on upper- or lower-body exercises? No Matter you
find yourself deciding, the secret is consistency and overload.
This weblog provides a woman’s information to gaining
muscle, full with a summary of key rules and a sample muscle-building exercise.
It’s confirmed that beginners tend to get the most muscle progress from exercising to failure.
This primary weightlifting routine ensures your
muscle tissue work to failure every workout.
Repeat this superset for a total of 3 sets to wrap up your week of coaching
(and week of full body exercise routine). First up in Exercise three
of our full body exercise program, we’ve the seated dumbbell shoulder press for three sets of 8-12 reps, which will primarily goal the entrance part of your shoulders.
If you need to lose fats or simply keep lean, cardio is a must.
Calories burned when weightlifting, particularly with a bro cut up, merely can’t
evaluate to conventional cardio.
That means you’ll spend lots of time working towards these
lifts and doing help workouts that might allow you to increase your energy
even additional in those three. You will doubtless gain muscle mass too,
but as a secondary impact to all the strength-oriented coaching you
will be doing. Some have specific targets (like increasing your bench press strength), while others are basic resistance training applications that will each improve your strength and
build muscle.
Analysis has proven that older adults who include
power coaching of their routines see higher total health outcomes
than those who avoid it. The Romanian deadlift is
a hip-hinge motion that builds the posterior chain—the hamstrings, glutes, and lower back.
You front squat energy gains instantly carry over to Olympic weightlifting, the clear
& jerk particularly. The receiving position in the clean is essentially a front squat.
Nevertheless, that doesn’t imply you need to solely do
entrance squats and not back squats.
As you’ll be able to see, the entire set of programming takes about 6 months to work
through. This is strictly what the concept behind minimalist
coaching is all about — stripping away the cruft and spending
essentially the most effort and vitality
on no matter provides you the most advantages. Similarly, a exercise app
providing or allowing you to set a component of problem will help you challenge yourself and encourage you to keep
enhancing to attain those challenges. Your selection will
largely decide your experience and the outcomes of the exercises.
There will be details on the coaches’ experience, qualifications, interests, approach
to fitness, etc., to assist you determine on one
of the best fit. An interesting feature is that you get to choose on your
professional trainer out of these matches, and also you get lots of choices.
It’s necessary to concentrate on security whenever you start a weight
training routine. Pay shut consideration to your body and resist the urge to push your self too rapidly.
Nevertheless, if you wish to construct up muscle mass, you’ll need to
do more repetitions and more frequent exercises.
Kettlebells, which are weighted balls with handles, are one other popular option.
You need not spend hours a day lifting weights to profit from strength coaching.
You can see vital improvement in your energy with
simply two or three 20- or 30-minute strength training sessions a week.
You could additionally be especially thinking about constructing your biceps or toning your legs, however one of the best resistance training program works
all the main muscle teams in your physique. Some exercises, including bicep curls and squats, can help weight coaching at residence or the health club.
You can use free weights or your physique weight with certain exercises to provide resistance.
Some coaches say high-volume training is finest for muscular hypertrophy.
It can be greatest for people who find themselves excessively busy with their work
or travel more often than not. A well-designed weight-training workout for a 60-year-old man contains more than just going into the fitness center and lifting weights.
It contains workout routines that improve balance, stability, agility and mobility.
In addition to energy, these elements won’t only make you fitter, however will improve
your day by day functioning and decrease your
threat of falls and different frequent age-related mishaps.
This is a 12 week Olympic weightlifting program with three to six training days per week, relying upon your classification. It can be utilized by beginner, intermediate, and advanced weightlifters, because it provides programming for
multiple lifter classifications. It trains all kinds of compound and isolation movements to construct energy
and develop muscle mass.
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