Описание
Основой препарата Гливек является действующее вещество Иматиниб — низкомолекулярный ингибитор протеинтирозинкиназы. Действие лекарства основано на ингибировании особого фермента, необходимого для развития клетки опухоли. После приема лекарства, злокачественные клетки начинают погибать.
In vitro иматиниб ингибирует пролиферацию и индуцирует апоптоз патологических клеток.
В исследованиях in vivo на животных моделях с использованием Bcr-Abl-позитивных опухолевых клеток, было показано, что вещество иматиниб обладает противоопухолевой способностью и при монотерапии. Иматиниб подавляет пролиферацию и вызывает апоптоз клеток стромальных опухолей ЖКТ, экспрессирующих тирозинкиназу с мутацией c-Kit рецептора, также он подавляет действие фактора роста стволовых клеток и фактора роста тромбоцитов, а также подавляет клеточные реакции, опосредуемые вышеназванными факторами.
Состав Гливек (Иматиниб)
1 капсула содержит:
- Действующее вещество: иматиниба мезилат 119,5 мг, что соответствует 100 мг иматиниба.
- Вспомогательные вещества: целлюлоза микрокристаллическая, диоксид кремния коллоидный безводный, кросповидон, диоксид титана, стеарат магния, желатин, краситель железа оксид желтый, краситель железа оксид красный.
- Состав чернил: краситель железа оксид красный, шеллак, лецитин соевый.
Показания к применению Гливек (Иматиниб)
- хронический миелолейкоз;
- острый лимфобластный лейкоз в составе химиотерапии и как монотерапия;
- миелодиспластические/миелопролиферативные, связанные с активацией рецептора тромбоцитарного фактора роста;
- системный мастоцитоз (с отсутствием D816V), c-Kit мутацией или при отсутствии данных о мутационном статусе c-Kit;
- гиперэозинофильный синдром и/или хроническая эозинофильная лейкемия у взрослых;метастатические стромальные опухоли органов ЖКТ;
- метастатические дерматофибросаркомы бугорковые.
Фармакодинамика
Иматиниб выраженно подавляет активность таких ферментов как BCR-ABL тирозинкиназы, рецепторов домена дискоитина (DDR1 и DDR2), KIT рецептора роста стволовых клеток, тромбоцитарного фактора роста альфа и бета (PDGFR-α и PDGFR-ß), колирующуюся KIT-протоонкогеном, рецептора колониестимулирующего фактора. Также Иматиниб может ингибировать клеточные процессы, запускаемые активацией этих рецепторных тирозинкиназ.
In vivo и in vitro иматиниб способен избирательно подавляеть действие фермента Bcr-Abl-тирозинкиназу на клеточном уровне, что влечет за собой ингибирование пролиферации у патологических клеток и вызывает апоптоз у клеточных линий, экспрессирующих Bcr-Abl-тирозинкиназу, включая незрелые лейкозных клеток при остром лимфобластном лейкозе и при хроническом миелолейкозе с положительной филадельфийской хромосомой.
Также, иматиниб является ингибитором рецепторов фермента тирозинкиназы для фактора стволовых клеток и фактора роста тромбоцитов, а также подавляет клеточные реакции, опосредуемые вышеназванными факторами.
Иматиниб подавляет пролиферацию и вызывает апоптоз клеток стромальных опухолей ЖКТ, экспрессирующих тирозинкиназу с мутацией c-Kit рецептора.
Фармакокинетика Гливек (Иматиниб)
Фармакокинетические величины иматиниба рассчитывались в диапазоне доз от 25 до 1000 мг. Фармакокинетические профили рассматривались в первый день, а также при достижении равновесного состояния иматиниба в плазме на 7-й или 28-й день.
Абсорбция.
После приема внутрь биодоступность препарата составляет в среднем 98%. Коэффициент вариации для показателя AUC составляет 40–60%. Существует прямая линейная зависимость значения AUC от величины дозы, в диапазоне доз от 25 до 1000 мг. При приеме лекарства с едой с высоким содержанием жиров, в сравнении с приемом натощак, отмечается незначительное уменьшение степени всасывания (уменьшение Cmax иматиниба в плазме крови на 11%, AUC — на 7,4%) и замедление скорости всасывания (увеличение Tmax иматиниба в плазме крови на 1,5 часа).
Распределение Гливек (Иматиниб) .
Исходя из полученных данных в исследованиях in vitro, при клинически значимых концентрациях иматиниб на 95% связывается с белками плазмы крови, в основном с альбумином и альфа-кислотным-гликопротеином, и в меньшей степени — с липопротеином.
Метаболизм.
Метаболизм иматиниба осуществляется главным образом, в печени с помощью изофермента CYP3A4, с образованием основного метаболита (N-деметилированное пиперазиновоое производное), циркулирующего в кровяном русле. In vitro данный метаболит иматиниба характеризуется фармакологической активностью, сходной с активностью исходного вещества. Значение AUC метаболита составляет 16% от AUC иматиниба. Степень связывания N-деметилированного метаболита с белками плазмы крови подобно таковому для иматиниба (аналогична степени связывания исходного соединения)
Выведение Гливек (Иматиниб).
После использования одной дозы иматиниб выводится из организма в течение 7 дней, преимущественно в виде метаболитов (68% — кишечником и 13% — почками). В неизмененном виде выводится около 25% дозы (20% — кишечником и 5% — почками). Период полувыведения иматиниба составляет около 18 часов.
При повторных приемах препарата раз в сутки, фармакокинетические параметры не меняются, а концентрация иматиниба становится больше исходной в 1,5–2,5 раза.
Фармакокинетика в особых клинических случаях
У больных старше 65 лет объем распределения повышается незначительно, только на 12%. Фармакокинетика иматиниба не зависит от пола, веса. Изменения данных клиренса и объема распределения иматиниба при одновременном приеме с другими ЛС незначительны и не требуют коррекции дозы.
У детей и подростков младше 18 лет, как и у взрослых пациентов, при приеме внутрь происходит быстрое всасывание препарата. AUC у детской группы пациентов в диапазоне доз 260 и 340 мг/м2 схожа с таковой у взрослых в диапазоне доз 400 и 600 мг. При сопоставлении у детей и подростков значений AUС на 1-й и 8-й дни после повторного приема препарата в дозе 340 мг/м2 раз в сутки отмечается увлечение значения этого показателя в 1,7 раза, что говорит о кумуляции иматиниба.
У больных с различными степенями нарушений функции печени средние значения AUC не повышаются. У больных с легкой или умеренной степенью тяжести функции почек (Cl креатинина >30 мл/мин) применение иматиниба отмечается увеличением экспозиции вещества в плазме в 1,5–2 раза, что соответствует повышению концентрации кислых альфа-гликопротеинов (основных белков плазмы, связывающихся с иматинибом). Препарат незначительно выводится почками. Клиренс свободного иматиниба одинаков как для пациентов с нарушениями функции почек, так и для здоровых добровольцев. Корреляции между тяжестью почечных нарушений и экспозицией препарата не выявлено.
Фармацевтические характеристики
Капсулы с порошком белого с желтоватым оттенком цвета:
- По 50 мг — от светло-желтого до оранжево-желтого оттенка, непрозрачные, размером №3. Имеют маркировку «NVR SH» красными чернилами.
- По 100 мг — от оранжевого до серовато-оранжевого цвета, непрозрачные, размером № 1. Имеют маркировку «NVR SI» красными чернилами.
Упаковка, срок годности, условия хранения
- Капсулы 50 мг. 10 шт. в блистере из ПВХ/ПЭ/ПВДХ. 3 блистера помещают в картонную пачку.
- Капсулы 100 мг. 12 шт. в блистере из ПВХ/ПЭ/ПВДХ. 2, 3, 4, 8, 10 и 15 блистеров помещают в картонную пачку.
По 12 капсул в блистере. 10 блистеров с инструкцией по применению в картонной коробке.
Материал блистера: ПВХ/алюминий (ПВХ/А1)
Хранить препарат необходимо при температуре не выше 30 °C, а также в недоступном для детей месте, .
Срок годности 2 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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To perform this exercise, you must place in entrance of
the cable machine and put ankle straps on the top of the cable.
How often you carry out leg workouts is decided by your health stage and objectives.
Nonetheless, it is not as efficient at constructing mass as a result
of it doesn’t permit as much weight to be lifted.
They can be carried out as cable-only leg exercises or as additions to different
leg workouts, but always remember that prioritizing progressive overload is necessary for power
gains. By customizing your leg workouts to align with your particular objectives, you’ll find
a way to successfully target the specified outcomes while
guaranteeing a well-rounded method to leg coaching.
Pistol squats are a popular bodyweight unilateral leg exercise, however boy, are they tough!
You don’t want a lot of fancy tools to coach your legs and
have a killer exercise. In fact, you’ll find a way to build muscle and power utilizing nothing more than dumbbells and bodyweight workout routines.
This exercise is right for residence exercisers,
and anytime you find yourself in a badly-equipped
gym. The leg curl machine is a staple in relation to leg
machines at the gym.
Your arms and core can also get extra toned over time with constant and ordinary rowing.
It also prompts the biceps and core muscle tissue and increases upper body
energy overall. Out of many, the Smith machine calf raise is a
wonderful train for developing sturdy and beefy calves.
Try to do 2-3 working units each leg day to assist build your energy on both legs.
The leg extension machine is particularly
designed to target the quadriceps, the dominant muscle group
on the front of the thigh. Equipped with a seat, backrest, and padded ankle lever, it provides resistance through an attached weight
stack.
The sumo squat is one other excellent variation on the standard squat.
As A End Result Of your ft are planted in a a lot wider stance (sumo stance), there is extra engagement of the
outer quads, glutes, and hamstrings. The hack squat exercise is an interesting variation of
the standard squat. With free weights, you need to fear so much
about your balance when squatting or lunging. Bear
In Mind how I mentioned that different muscular tissues have to interact to maintain stability?
The power diverted to those secondary stabilizer muscles means there’s less power to send to your legs.
This added stability makes it simpler for newbies to develop their squatting and lunging abilities, even when they’ve by
no means lifted weights.
They could be low-tech, however barbells are still probably
the greatest ways to construct muscle size and power.
This barbell solely exercise is perfect for these days if you need to use brute force
to lift heavy weights and embrace your inner powerlifter.
The bench may even elevate and decrease on the leg-side (rather than the higher physique facet, like the
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machine, permitting you to target the hamstrings.
It’s also safer and easier to regulate your foot positioning on the hack squat machine.
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the machine. The quadriceps muscle tissue are engaged and strengthened when the person extends their legs straight
out in entrance of them.
One of probably the most important factors is ensuring you’re not attempting
to lift extra weight than you want to. If you probably can’t control your movements,
you should scale back the load. Correct kind
is more necessary than the quantity of weight you’re lifting.
The age-old query, is the leg press higher than the squat,
is finest answered by saying no; they’re just completely different.
Now you presumably can knock out as many crunches as you want,
and the main focus will be on your higher abs (because your legs are braced/immobilized).
All you must do is flip round so you face upward as a substitute of down. Your legs can nonetheless be braced the same method they’re when you do glute-ham raises, and your butt/legs
will be resting on the thigh pad.
Whereas it’s not the most effective machine in the gym—it isolates your
abs muscle tissue, so it won’t enhance stability in your core—it’s an efficient way
to focus on your abs for a more effective, isolated exercise.
Use it as a «finisher» as quickly as you’ve accomplished all those planks, crunches,
and leg lifts. As A End Result Of the Smith machine
limits the range of movement, and the bar of the machine offers
poor grip. Nevertheless, you can still try a couple of
exercises to beef up your biceps. When it comes to constructing defined legs, training calves is equally necessary.
The drag curl completely isolates your biceps brachaii, working both
the short head and long head bicep muscles. Nevertheless, you should
be extremely careful with this movement as you’re put in a compromised place…and if you’re a man, it may depart you
in a bit of pain, if you understand what I mean. Nevertheless, the movement
can place plenty of pressure on the wrist, and elbow joints, so it’s
not for everyone. You can also print the PDF to keep a bodily copy of
the workout plan with you on the fitness center. Establish each
short-term and long-term health targets that are practical and align with your
aspirations. If yours does not, most of the employees must also know how to
use the machines, they usually can present you tips on how
to use them.
For the last of our cable machine exercises, we are going to carry out some standing cable calf raises to construct our calves.
We will begin off the leg day with some simple cable squats and cable leg extensions to construct our quadricep muscular tissues.
Each of these workout routines are fairly effective at targeting
the quadriceps whereas additionally activating other muscle teams in the
leg.
You’re unsupported, lifting up and down on your toes to have interaction the calf muscle.
Both variations of the train aim to focus on the muscle
tissue in the back of the decrease leg. The hack squat machine engages fewer muscle tissue than the common squat.
So, you’ll have the flexibility to lift more than you would when it’s just you and a barbell.
It’s suitable for these trying to the movement and to focus on the quads and hamstrings a little higher.
If you’ve injured your hamstring, you’re in for a
long recovery. Leg curl machines give you controlled actions that won’t jerk your
muscles and ligaments round.
Give this entire routine, modeled by IFBB bikini pro Rachelle DeJean, a
try—or sub in a few of your favorite moves on your next leg-day exercise for outcomes
you’ll love (and feel!). Tailor the provided plans to your health level
and goals, and remember to enjoy the journey toward a healthier, stronger you.
Planet Health is designed to be a supportive and judgment-free space, making it an ideal setting for people at
all stages of their health and fitness journey. With these in-depth insights, you can build an effective exercise
routine at Planet Fitness.
So we put our heads collectively and examined out a couple
of nice machine solely leg exercises, so we’re by no means left dissatisfied once more.
Many go for leg exercise machines to simplify leg day, streamlining their routines.
The leg press machine, a popular piece of fitness center tools, targets and strengthens many leg muscular tissues.
It includes a 45-degree reclined seat with a platform in your toes and an adjustable weighted
sled. The cable leg exercises are divided into squats, cable deadlifts, cable lunges,
and calf raises.
These muscular tissues are pivotal for actions like strolling, operating, and maintaining steadiness.
Constructing robust calves not only improves athletic prowess but additionally
offers crucial ankle stability. The volume of your workout program refers
again to the variety of units, reps, and workout routines performed in each
exercise. If you don’t have a platform to perform the standing cable one-leg calf
increase from, you can do it on the floor. It’s
an unconventional motion, but it’s very efficient for building the lower posterior chain muscles.
The cable standing leg curl is useful if you can’t entry a leg curl machine.
Here are thirteen of the most effective workout
routines for legs carried out on a cable pulley system fitness center.
A glute ham developer, generally known as the glute ham elevate or just GHD, is amongst the greatest machines for isolating a number of posterior chain muscles.
It tends to be favored by athletes such as powerlifters
who find that it presents good carry over to workout routines such because the barbell squat.
With the cable machine, you’ll have a flat resistance curve that creates fixed tension all through an exercise.
When we use the term range of motion, this refers to how far you’ll be able to
transfer your joints in several instructions. When you carry out exercises that move your joints through their
full range of motion, you will have larger
ends in hypertrophy and strength.
Nothing says «I hit the gym hard» like a set of ridiculously sculpted quads and calves—especially during beach season. However
let’s be trustworthy, you need to keep the muscle definition in your legs
all year round—whether you’re sporting a pair of swim trunks or the proper pair of denim denims.
Rowing machines are widely accepted as probably the greatest full-body exercise machines out there today!
A rower works round 90% of your body, making it a whole exercise machine.
The Smith machine is likely considered one of the safest items of kit in the fitness center.
The most vital difference between health club machines and free weights is that
with free weights, you presumably can select the place and how you progress with them.
The seat top, backrest angle, and foot location of some leg machines can all be adjusted.
Select a machine that might be adjusted to meet your body
sort and health degree in case you have any limitations or injuries.
The Smith machine can be used for numerous lower-body
exercises, including squats, lunges, and calf lifts.
This may help to spice up your exercise program and maintain issues fascinating.
Leg extension machines can also make an excellent addition to any
house health club.
This train strengthens the hamstrings, glutes, and decrease
again by focusing on the hip hinge motion. Cable lunges target the quads, glutes, and hamstrings while participating core stabilizers for steadiness.
Cable squats have interaction your quads, hamstrings, and glutes, including fixed resistance all through the movement.
A smith machine permits you to train to failure in relative safety
and leaves you free to focus in your mind-muscle connection because the
weights stability themselves. Olympic weightlifting bars weigh a normal
20 kilograms or forty five kilos. This makes it straightforward to work out how a lot weight you’re lifting,
even if you are coaching in a new fitness center.
Unfortunately, there is no such standardized weight for Smith machine bars, and they can weigh from as
little as 15 kilos to over 50.
Leg machines enable fast weight changes and clean transitions between workout routines.
Machines like the seated leg curl and leg extension machines require minimal setup, saving time
between exercises and sets. This efficiency helps preserve depth throughout leg workouts,
which is essential for muscle development and endurance. A plate loaded leg extension/curl machine is
a dual-function piece of health club equipment designed to focus on each the back and front of the thighs.
The standing leg curl machine is an effective selection if you would
like to train every leg independently from the opposite.
Whilst, this may be accomplished on the opposite two variations, the standing leg
curl is particularly designed for unilateral training making
it a little easier for range of movement. As its name suggests, it isolates the glutes and hamstrings while serving
to to strengthen the lower back. Whilst the glute ham
developer is less common in huge field and chain gyms, you’ll probably get access to 1 in gyms that target specific power sports activities such
as powerlifting and bodybuilding. Using leg machines two to 3 times
per week allows enough engagement and muscle recovery.
This managed motion reduces reliance on stabilizer muscles,
making it easier to develop power in isolated areas.
We may also provide tips about using these machines safely and successfully to get probably the most out of your exercises.
Whereas not particularly a leg machine, the Smith Machine is
among the hottest tools for doing lower physique workout routines like Smith Machine squats, lunges, deadlifts, and even hip thrusts.
You can even use a squat machine and cable
machines to strengthen your legs. The Calf Elevate Machine is designed to strengthen and target the calf
muscular tissues. It consists of a padded lever and a platform the place you place
your shoulders. This machine permits for controlled and isolated actions to work the calf muscles effectively.
Do Not worry concerning the opinions of others; focus
in your goals and what makes you comfy. Take advantage
of the assistance provided by Planet Health employees.
Whether Or Not you need steering on utilizing equipment or have questions on your workout routine, they are there to help.
Stick to your chosen exercise program consistently to
see long-term results. Set Up a realistic and sustainable
workout routine with the identical workout that fits your schedule and preferences.
Make certain to gas your body with a well-balanced food regimen wealthy in carbohydrates, protein, healthy fats, vitamins, and minerals.
A leg train machine (also known as a lower physique exercise machine) is a bit
of fitness tools specifically designed to work the leg muscular tissues.
These machines come in numerous styles and sizes, each targeting different muscle teams in your decrease physique.
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stage. Unlike free-weight exercises that require good form and
stability, lower body workout machines provide more stability and assist throughout your workout.
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